bims-drumid 2024-12-22 papers

bims-drumid

Biomed News

on Drugs for mitochondrial diseases

Issue of 2024–12–22
twenty papers selected by
Volkmar Weissig, Midwestern University

Targeting mitochondrial dynamics: A promising approach for intracerebral hemorrhage therapy.
Mitochondrial Dynamics in Brain Cells During Normal and Pathological Aging.
Mitochondrial transfer of drug-loaded artificial mitochondria for enhanced anti-Glioma therapy through synergistic apoptosis/ferroptosis/immunogenic cell death.
Exercise as Mitochondrial Medicine: How Does the Exercise Prescription Affect Mitochondrial Adaptations to Training?
Extracellular vesicles as standard-of-care therapy: will fast-tracking the regulatory processes help achieve the goal?
Neuronal Cell Rearrangement During Aging: Antioxidant Compounds as a Potential Therapeutic Approach.
Current Update on Promising New Anti-Alzheimer's Drugs in Different Phases of Clinical Development: Where Exactly Are We Lacking?
Chiral nanosystem and chiral supraparticles for drug delivery: an expert opinion.
The use of nanocarriers in treating Batten disease: A systematic review.
Vanadium Complexes for Mitochondria-Targeted Photodynamic Therapy.
Advanced Delivery Systems and Novel Psilocin Derivatives for Enhanced Therapeutic Applications.
Biodistribution of therapeutic extracellular vesicles.
Anti-amyloid treatments in Alzheimer's disease: elegance, evidence and ethics.
Antioxidants in neuropsychiatric disorder prevention: neuroprotection, synaptic regulation, microglia modulation, and neurotrophic effects.
ROS Regulation in CNS Disorder Therapy: Unveiling the Dual Roles of Nanomedicine.
Examining the role of antioxidant supplementation in mitigating oxidative stress markers in Alzheimer's disease: a comprehensive review.
Mapping mitochondrial aging.
Mitochondrial DNA Damage and Its Repair Mechanisms in Aging Oocytes.
Secretome - the role of extracellular vesicles in the pathogenesis and therapy of neurodegenerative diseases.
The antioxidant barrier, oxidative/nitrosative stress, and protein glycation in allergy: from basic research to clinical practice.

Life Sci. 2024 Dec 12. pii: S0024-3205(24)00907-X. [Epub ahead of print] 123317

Targeting mitochondrial dynamics: A promising approach for intracerebral hemorrhage therapy.

Mengnan Liu, Binru Li, Zhixue Yin, Lu Yin, Ye Luo, Qi Zeng, Dechou Zhang, Anguo Wu, Li Chen.

  Intracerebral hemorrhage (ICH) is a major global health issue with high mortality and disability rates. Following ICH, the hematoma exerts direct pressure on brain tissue, and blood entering the brain directly damages neurons and the blood-brain barrier. Subsequently, oxidative stress, inflammatory responses, apoptosis, brain edema, excitotoxicity, iron toxicity, and metabolic dysfunction around the hematoma further exacerbate brain tissue damage, leading to secondary brain injury (SBI). Mitochondria, essential for energy production and the regulation of oxidative stress, are damaged after ICH, resulting in impaired ATP production, excessive reactive oxygen species (ROS) generation, and disrupted calcium homeostasis, all of which contribute to SBI. Therefore, a central factor in SBI is mitochondrial dysfunction. Mitochondrial dynamics regulate the shape, size, distribution, and quantity of mitochondria through fusion and fission, both of which are crucial for maintaining their function. Fusion repairs damaged mitochondria and preserves their health, while fission helps mitochondria adapt to cellular stress and removes damaged mitochondria through mitophagy. When this balance is disrupted following ICH, mitochondrial dysfunction worsens, oxidative stress and metabolic failure are exacerbated, ultimately contributing to SBI. Targeting mitochondrial dynamics offers a promising therapeutic approach to restoring mitochondrial function, reducing cellular damage, and improving recovery. This review explores the latest research on modulating mitochondrial dynamics and highlights its potential to enhance outcomes in ICH patients.

Keywords:  Intracerebral hemorrhage; Mitochondrial dynamics; Mitochondrial fission; Mitochondrial fusion; Neuroprotection strategies; Secondary brain injury

DOI:  https://doi.org/10.1016/j.lfs.2024.123317
Int J Mol Sci. 2024 Nov 29. pii: 12855. [Epub ahead of print]25(23):

Mitochondrial Dynamics in Brain Cells During Normal and Pathological Aging.

Vladimir S Sukhorukov, Tatiana I Baranich, Anna V Egorova, Anastasia V Akateva, Kseniia M Okulova, Maria S Ryabova, Krisitina A Skvortsova, Oscar V Dmitriev, Natalia M Mudzhiri, Dmitry N Voronkov, Sergey N Illarioshkin.

  Mitochondrial dynamics significantly play a major role in the pathogenesis of neurodegenerative diseases, such as Parkinson's disease and Alzheimer's disease. The dysregulation of mitochondrial biogenesis and function, characterized by impaired fission and fusion processes mediated by a number of proteins, in particular, Drp1, Mfn1, Mfn2, Opa1, and PGC-1α, contributes to neuronal vulnerability and degeneration. Insufficient mitophagy and disrupted mitochondrial transport exacerbate oxidative stress and neurotoxicity. Emerging therapeutic strategies that target mitochondrial dynamics, including various pharmacological agents, demonstrate potential for restoring mitochondrial balance and enhancing neuroprotection. This growing body of research underscores the importance of mitochondrial health in developing effective interventions for neurodegenerative conditions. This review highlights well-established links between the disruption of mitochondrial dynamics and the development of neurodegenerative processes. We also discuss different therapeutic strategies that target mitochondrial function in neurons that have been proposed as perspective neuroprotective treatments.

Keywords:  mitochondrial dynamics; mitophagy; neurodegeneration; neuroprotection

DOI:  https://doi.org/10.3390/ijms252312855
Acta Biomater. 2024 Dec 12. pii: S1742-7061(24)00738-4. [Epub ahead of print]

Mitochondrial transfer of drug-loaded artificial mitochondria for enhanced anti-Glioma therapy through synergistic apoptosis/ferroptosis/immunogenic cell death.

Mingzhu Song, Jiayu Yuan, Ge Zhang, Mengdi Sun, Yifei Zhang, Xiangchen Su, Ruizhen Lv, Yuting Zhao, Yijie Shi, Liang Zhao.

  Mitochondrial targeting in gliomas represents a novel therapeutic strategy with significant potential to enhance drug sensitivity by effectively leveraging the inherent vulnerabilities of glioma cells at the mitochondrial level. In this study, we developed a sophisticated nano-delivery system by engineering artificial mitochondria from mitochondrial membrane-based nanovesicles, enabling precise targeting of doxorubicin (Dox) to selectively eradicate cancer cells while amplifying multiple cell death pathways. It was found that Dox-encapsulating mitochondria-based nanovesicles (DOX-MitoNVs) have exhibited an extraordinary ability to penetrate the blood-brain barrier (BBB), specifically targeting gliomas. By targeting mitochondria instead of infiltrating the nucleus, DOX-MitoNVs not only amplified Dox mediated apoptosis effects through the overload of intracellular Ca2+ but also intensified ferroptosis by generating reactive oxygen species (ROS). Furthermore, DOX-MitoNVs demonstrated a significant ability to modulate the tumor immune microenvironment, thereby inducing pronounced immunogenic cell death (ICD) effects. In summary, it presents a novel therapeutic strategy utilizing DOX-MitoNVs for precise mitochondrial targeting in gliomas, enhancing drug sensitivity, inducing multiple cell death pathways, and modulating the tumor immune microenvironment to promote immunogenic cell death. STATEMENT OF SIGNIFICANCE: Mitochondrial targeting in gliomas is a promising therapeutic strategy that enhances drug sensitivity by exploiting glioma cells' mitochondrial vulnerabilities. We engineered artificial mitochondria from mitochondrial membrane-based nanovesicles as a novel nano-delivery system for precise targeting of Doxorubicin (Dox). This approach facilitates selective cancer cell eradication and amplifies multiple cell death pathways alongside immunogenic chemotherapy. Notably, Dox-encapsulating mitochondria-based nanovesicles (DOX-MitoNVs) effectively cross the blood-brain barrier (BBB) and specifically target gliomas. By focusing on mitochondria, Dox induces apoptosis and intensifies ferroptosis through reactive oxygen species (ROS) generation. Additionally, DOX-MitoNVs can transform the tumor immune microenvironment, promoting immunogenic cell death (ICD). Overall, DOX-MitoNVs offer a compelling platform for enhanced glioma therapy.

Keywords:  ICD; Mitochondria; apoptosis; doxorubicin; ferroptosis; nanovesicles

DOI:  https://doi.org/10.1016/j.actbio.2024.12.027
Annu Rev Physiol. 2024 Dec 10.

Exercise as Mitochondrial Medicine: How Does the Exercise Prescription Affect Mitochondrial Adaptations to Training?

David J Bishop, Matthew J-C Lee, Martin Picard.

Mitochondria are multifaceted organelles with several life-sustaining functions beyond energy transformation, including cell signaling, calcium homeostasis, hormone synthesis, programmed cell death (apoptosis), and others. A defining aspect of these dynamic organelles is their remarkable plasticity, which allows them to sense, respond, and adapt to various stressors. In particular, it is well-established that the stress of exercise provides a powerful stimulus that can trigger transient or enduring changes to mitochondrial molecular features, activities, integrated functions, behaviors, and cell-dependent mitochondrial phenotypes. Evidence documenting the many beneficial mitochondrial adaptations to exercise has led to the notion of exercise as a mitochondrial medicine. However, as with other medicines, it is important to understand the optimal prescription (i.e., type, dose, frequency, duration). In this review, we build on a systematic biological framework that distinguishes between domains of mitochondrial biology to critically evaluate how different exercise prescription variables influence mitochondrial adaptations to training.

DOI: https://doi.org/10.1146/annurev-physiol-022724-104836
Regen Med. 2024 Dec 17. 1-19

Extracellular vesicles as standard-of-care therapy: will fast-tracking the regulatory processes help achieve the goal?

Vaijayanti Kale.

  Extracellular Vesicles (EVs) became a focus of clinical research when experimental and pre-clinical studies showed that they mimic their parent cells' regenerative and therapeutic effects and their cargo carries disease-specific diagnostic and prognostic biomarkers. Since the publication of data forms an endpoint of the study, this review specifically focused on the published clinical trials done with EVs. For brevity, this review was restricted to the last 10 years. Unexpectedly, the literature search showed that very few clinical trials assessing the therapeutic applications of EVs were published in this period indicating that they have not reached their desired endpoint. Conversely, most studies showed the potential of EVs present in various biofluids as a promising source of diagnostic and prognostic biomarkers for various diseases, and predictive markers to assess the effectiveness of therapy. This stark difference in the numbers could perhaps be due to the time-consuming regulatory processes involved in the clinical-grade preparation and characterization of EVs, and the determination of their safety and effective dose regimens. One wonders whether fast-tracking regulatory affairs could help accelerate the therapeutic use of EVs. This aspect needs urgent attention.

Keywords:  Extracellular vesicles; Regulatory processes; biomarkers; clinical trials; therapeutic

DOI:  https://doi.org/10.1080/17460751.2024.2442847
Cells. 2024 Nov 23. pii: 1945. [Epub ahead of print]13(23):

Neuronal Cell Rearrangement During Aging: Antioxidant Compounds as a Potential Therapeutic Approach.

Erjola Bej, Patrizia Cesare, Michele d'Angelo, Anna Rita Volpe, Vanessa Castelli.

  Aging is a natural process that leads to time-related changes and a decrease in cognitive abilities, executive functions, and attention. In neuronal aging, brain cells struggle to respond to oxidative stress. The structure, function, and survival of neurons can be mediated by different pathways that are sensitive to oxidative stress and age-related low-energy states. Mitochondrial impairment is one of the most noticeable signs of brain aging. Damaged mitochondria are thought to be one of the main causes that feed the inflammation related to aging. Also, protein turnover is involved in age-related impairments. The brain, due to its high oxygen usage, is particularly susceptible to oxidative damage. This review explores the mechanisms underlying neuronal cell rearrangement during aging, focusing on morphological changes that contribute to cognitive decline and increased susceptibility to neurodegenerative diseases. Potential therapeutic approaches are discussed, including the use of antioxidants (e.g., Vitamin C, Vitamin E, glutathione, carotenoids, quercetin, resveratrol, and curcumin) to mitigate oxidative damage, enhance mitochondrial function, and maintain protein homeostasis. This comprehensive overview aims to provide insights into the cellular and molecular processes of neuronal aging and highlight promising therapeutic avenues to counteract age-related neuronal deterioration.

Keywords:  ROS; antioxidants; brain; mitochondrial dysfunction; neurodegeneration; organelles; oxidative damage

DOI:  https://doi.org/10.3390/cells13231945
J Assoc Physicians India. 2024 Dec;72(12): 49-54

Current Update on Promising New Anti-Alzheimer's Drugs in Different Phases of Clinical Development: Where Exactly Are We Lacking?

Pramod Kumar Sharma, Mamta Yadav, Neeraj Mehta.

The prevalence of Alzheimer's disease (AD) is rising with an aging population worldwide and is expected to surpass 130 million by 2050. India is no exception, but the true prevalence data on AD is not conclusive. By 2050, India will have almost 15% of the population aged 60 years or above. It is the need of the hour to have newer and more effective agents that can address various therapeutic needs of Alzheimer's viz., halt or delay disease progression, and offer better improvement in symptomatology. The most desirable would be to have an intervention that can prevent AD onset. The prime focus of the present review is to introduce to the readers the promising drug candidates across the world. We reviewed all the information available to us through a literature search. It is quite apparent that the developmental efforts are concentrated not only on disease-modifying therapies that can prevent the development but also on palliative therapies that improve the quality of life of AD patients. Several approaches including biological and small molecules are being explored to tap their potential in AD therapeutics using sound scientific research principles and execution. Besides conventional development approaches, the drug repurposing strategy has emerged as quick, cost-effective, and less risky and is being exploited to the fullest. The drugs in the pipeline and undergoing various phases of clinical trials for the past 5 years are taken from the ClinicalTrials.gov registry. It remains to be seen the advent of a successful disease-modifying agent for AD in future.

DOI: https://doi.org/10.59556/japi.72.0755
Expert Opin Drug Deliv. 2024 Dec 17.

Chiral nanosystem and chiral supraparticles for drug delivery: an expert opinion.

Mahfoozur Rahman, Janhvi Singh, Alhussain Aodah, Majed Alrobaian, Nabil K Alruwaili, Waleed H Almalki, Salem Salman Almujri, Safia Obaidur Rab, Osama A Madkhali, Ankit Sahoo, Jonathan A Lal.

Introduction Chiral nanocarriers enhance therapeutic efficacy by improving in vivo stability and cellular uptake. Chemical functionalization reduces cytotoxicity, resulting in favorable biocompatibility. Nanoparticles self-assemble into supraparticles, enhancing drug delivery through improved retention and drug loading. Area covered This review covers chiral nanostructures and chiral supraparticles, their mechanisms, and their applications in drug delivery and various healthcare applications. Expert Opinion The chirality of biomaterials is crucial for advancing nanomedicine. Chiral nanosystem enhance drug delivery by interacting selectively with biological molecules, improving their specificity and efficacy. This reduces off-target effects and improves therapeutic outcomes. Research has focused on cellular uptake and elimination to ensure safety, and chiral nanomaterials also show promise in optical sensing and gene editing. Their biocompatibility and ability to self-assemble into supraparticles may make them ideal for drug delivery systems.

DOI: https://doi.org/10.1080/17425247.2024.2444347
Int J Pharm. 2024 Dec 16. pii: S0378-5173(24)01328-0. [Epub ahead of print] 125094

The use of nanocarriers in treating Batten disease: A systematic review.

Larissa Henke, Ali Ghorbani, Sara E Mole.

  The neuronal ceroid lipofuscinoses, commonly known as Batten disease, are a group of lysosomal storage disorders affecting children. There is extensive central nervous system and retinal degeneration, resulting in seizures, vision loss and a progressive cognitive and motor decline. Enzyme replacement and gene therapies are being developed, and mRNA and oligonucleotide therapies are more recently being considered. Overcoming the challenges of the blood-brain barrier and blood-ocular barrier is crucial for effectively targeting the brain and eye, whatever the therapeutic approach. Nanoparticles and extracellular vesicles are small carriers that can encapsulate a cargo and pass through these cell barriers. They have been investigated as drug carriers for other pathologies and could be a promising treatment strategy for Batten disease. Their use in gene, enzyme, or mRNA replacement therapy of all lysosomal storage disorders, including Mucopolysaccharidoses, Niemann-Pick diseases, and Fabry disease, is investigated in this systematic review. Different nanocarriers can efficiently target the lysosome and cross the barriers into the brain and eyes. This supports continued exploration of nanocarriers as potential future treatment options for Batten disease.

Keywords:  Batten disease; Blood-brain barrier; Lysosomal storage diseases; Nanomedicine

DOI:  https://doi.org/10.1016/j.ijpharm.2024.125094
Chembiochem. 2024 Dec 17. e202400901

Vanadium Complexes for Mitochondria-Targeted Photodynamic Therapy.

Md Kausar Raza, Arun Kumar.

  This minireview focuses on vanadium complexes in photodynamic therapy (PDT), particularly for their potential as mitochondria-targeted anticancer agents. Vanadium's coordination versatility supports its bioactivity, showing promise in insulin-mimetic, lipid-lowering, and antitumor effects. PDT leverages these complexes' redox properties, producing reactive oxygen species (ROS) within mitochondria to induce cancer cell apoptosis with minimal impact on healthy cells. The review covers design strategies to improve mitochondrial localization, photodynamic efficiency, and selective cytotoxicity while addressing challenges like photostability and targeting for next-gen PDT applications.

Keywords:  Bioinorganic, Vanadium, Mitochondria, Anticancer, Photodynamic Therapy

DOI:  https://doi.org/10.1002/cbic.202400901
ACS Med Chem Lett. 2024 Dec 12. 15(12): 2080-2082

Advanced Delivery Systems and Novel Psilocin Derivatives for Enhanced Therapeutic Applications.

Robert B Kargbo.

Psychedelic compounds, particularly psilocybin and psilocin, have shown significant therapeutic potential in treating neurological and psychiatric disorders. However, their bioavailability, rapid metabolism, and stability challenges have limited their clinical use. This Patent Highlight reviews recent innovations in psychedelic drug delivery systems and the development of psilocin analogs aimed at improving their pharmacokinetic and pharmacodynamic profiles. Three patents-focused on controlled-release delivery systems, ester analogs, and acetal/ketal derivatives-present novel approaches to enhancing the stability, bioavailability, and efficacy of psilocin and related compounds. These advancements promise more effective treatments for conditions such as depression, chronic pain, and neurodegenerative diseases.

DOI: https://doi.org/10.1021/acsmedchemlett.4c00521
Extracell Vesicles Circ Nucl Acids. 2023 ;4(2): 170-190

Biodistribution of therapeutic extracellular vesicles.

Dhanu Gupta, Oscar P B Wiklander, Matthew J A Wood, Samir El-Andaloussi.

  The field of extracellular vesicles (EVs) has seen a tremendous paradigm shift in the past two decades, from being regarded as cellular waste bags to being considered essential mediators in intercellular communication. Their unique ability to transfer macromolecules across cells and biological barriers has made them a rising star in drug delivery. Mounting evidence suggests that EVs can be explored as efficient drug delivery vehicles for a range of therapeutic macromolecules. In contrast to many synthetic delivery systems, these vesicles appear exceptionally well tolerated in vivo. This tremendous development in the therapeutic application of EVs has been made through technological advancement in labelling and understanding the in vivo biodistribution of EVs. Here in this review, we have summarised the recent findings in EV in vivo pharmacokinetics and discussed various biological barriers that need to be surpassed to achieve tissue-specific delivery.

Keywords:  CNS targeting; Exosomes; extracellular vesicles; in vivo biodistribution; targeted delivery

DOI:  https://doi.org/10.20517/evcna.2023.12
Adv Clin Exp Med. 2024 Dec 19.

Anti-amyloid treatments in Alzheimer's disease: elegance, evidence and ethics.

Timothy Daly, Andi Olluri, Markku Kurkinen.

  The so-called "amyloid cascade hypothesis" provides an elegant explanation of Alzheimer's disease (AD), has motivated the amyloid-lowering therapeutic strategy, and led to the elaboration of a rich experimental and conceptual toolkit for the field to progress. But it might be incorrect. The scientific evidence base supporting the efficacy and safety of current anti-amyloid antibody treatments in AD is weak. Nevertheless, we argue that there is a bias towards the amyloid-lowering therapeutic strategy amongst key opinion leaders in the research and advocacy communities. To demonstrate this, we first focus on the AD lexicon: while any accrual of amyloid on a brain PET scan can now permit diagnosis/definition of AD, lowering positron emission tomography (PET) amyloid is considered disease modification, and treatment-induced side-effects are hidden behind neutral-sounding acronyms: ARIA (amyloid-β (Aβ)-related imaging abnormalities: brain bleeding and swelling) and ARPA (amyloid-β (Aβ) removal-related pseudo-atrophy: brain shrinkage). Second, we underline that drugmakers did not test anti-amyloid antibodies against the best proven interventions and did not adequately inform trial participants of risks, thus violating research ethics of the Declaration of Helsinki on 2 counts. In conclusion, we are critical of over-reliance on the idea that PET amyloid-lowering treatments for AD are a therapeutic revolution as claimed, and consider that optimism does not excuse a lack of scientific, regulatory, and ethical integrity. We argue for rigorous, properly controlled (e.g. donepezil) anti-amyloid trials demonstrating cognitive and functional benefit before accepting amyloid-lowering drugs as the new standard of care for AD patients.

Keywords:  Alzheimer’s disease; amyloid hypothesis; bias; clinical trials; ethics

DOI:  https://doi.org/10.17219/acem/198674
Front Neurosci. 2024 ;18 1505153

Antioxidants in neuropsychiatric disorder prevention: neuroprotection, synaptic regulation, microglia modulation, and neurotrophic effects.

Fangfei Liu, Qianqian Bai, Wenchao Tang, Shumin Zhang, Yan Guo, Shunji Pan, Xiaoyu Ma, Yanhui Yang, Hua Fan.

  Oxidative stress, caused by an imbalance between the generation of reactive oxygen species (ROS) and the body's intrinsic antioxidant defenses, plays a critical role in neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's. Beyond these conditions, recent evidence indicates that dysregulated redox balance is implicated in neuropsychiatric disorders, including schizophrenia, major depressive disorder, and anxiety disorders. Preclinical and clinical studies have demonstrated the potential of antioxidants, such as N-acetylcysteine, sulforaphane, alpha-lipoic acid, L-carnitine, ascorbic acid, selenocompounds, flavones and zinc, in alleviating neuropsychiatric symptoms by mitigating excitotoxicity, enhancing synaptic plasticity, reducing microglial overactivation and promoting synaptogenesis. This review explores the role of oxidative stress in the pathogenesis of neuropsychiatric disorders. It provides an overview of the current evidence on antioxidant therapy's pharmacological effects, as demonstrated in animal models and clinical studies. It also discusses the underlying mechanisms and future directions for developing antioxidant-based adjuvant therapies. Given the limitations and side effects of existing treatments for neuropsychiatric disorders, antioxidant therapy presents a promising, safer alternative. Further research is essential to deepen our understanding and investigate the clinical efficacy and mechanisms underlying these therapies.

Keywords:  antioxidants; microglia modulation; neuroprotection; neuropsychiatric disorders; neurotrophic effects; oxidative stress; synaptic regulation

DOI:  https://doi.org/10.3389/fnins.2024.1505153
Small. 2024 Dec 15. e2410031

ROS Regulation in CNS Disorder Therapy: Unveiling the Dual Roles of Nanomedicine.

Zhengyang Quan, Sa Wang, Huanhuan Xie, Jiayi Zhang, Ranran Duan, Menglin Li, Jinfeng Zhang.

  The treatment of brain diseases has always been the focus of attention. Due to the presence of the blood-brain barrier (BBB), most small molecule drugs are difficult to reach the brain, leading to undesirable therapeutic outcomes. Recently, nanomedicines that can cross the BBB and precisely target lesion sites have emerged as thrilling tools to enhance the early diagnosis and treat various intractable brain disorders. Extensive research has shown that reactive oxygen species (ROS) play a crucial role in the occurrence and progression of brain diseases, including brain tumors and neurodegenerative diseases (NDDs) such as Alzheimer's disease, Parkinson's disease, stroke, or traumatic brain injury, making ROS a potential therapeutic target. In this review, on the structure and function of BBB as well as the mechanisms are first elaborated through which nanomedicine traverses it. Then, recent studies on ROS production are summarized through photodynamic therapy (PDT), chemodynamic therapy (CDT), and sonodynamic therapy (SDT) for treating brain tumors, and ROS depletion for treating NDDs. This provides valuable guidance for the future design of ROS-targeted nanomedicines for brain disease treatment. The ongoing challenges and future perspectives in developing nanomedicine-based ROS management for brain diseases are also discussed and outlined.

Keywords:  BBB; Brain tumors; ROS regulation; nanomedicine; neurodegenerative disorders

DOI:  https://doi.org/10.1002/smll.202410031
Inflammopharmacology. 2024 Dec 19.

Examining the role of antioxidant supplementation in mitigating oxidative stress markers in Alzheimer's disease: a comprehensive review.

Mahmood Jawad, Subasini Uthirapathy, Farag M A Altalbawy, Enwa Felix Oghenemaro, Jasur Rizaev, Madan Lal, Mamdouh Eldesoqui, Naveen Sharma, Atreyi Pramanik, Ahmed Khudhair Al-Hamairy.

  Alzheimer's disease is a devastating neurodegenerative disorder that affects millions of people worldwide. One of the key pathological features of Alzheimer's disease is oxidative stress, which is characterized by an imbalance between the production of reactive oxygen species and the body's ability to neutralize them with antioxidants. In recent years, there has been growing interest in the potential role of antioxidant supplementation in mitigating oxidative stress markers in Alzheimer's disease. This review paper aims to provide a comprehensive overview of the current research on antioxidant supplementation in Alzheimer's disease and its effects on oxidative stress markers. The paper will examine the underlying mechanisms of oxidative stress in Alzheimer's disease, the potential benefits of antioxidant supplementation, and the challenges and limitations of using antioxidants as a therapeutic strategy.

Keywords:  Alzheimer’s disease; Antioxidants; Neuroprotection; Oxidative stress; Reactive oxygen species

DOI:  https://doi.org/10.1007/s10787-024-01622-9
Elife. 2024 Dec 20. pii: e105191. [Epub ahead of print]13

Mapping mitochondrial aging.

Alessandro Bitto.

  Measuring mitochondrial respiration in frozen tissue samples provides the first comprehensive atlas of how aging affects mitochondrial function in mice.

Keywords:  aging; cellular respiration; computational biology; mitochondria; mouse; respiration atlas; sex; systems biology

DOI:  https://doi.org/10.7554/eLife.105191
Int J Mol Sci. 2024 Dec 06. pii: 13144. [Epub ahead of print]25(23):

Mitochondrial DNA Damage and Its Repair Mechanisms in Aging Oocytes.

Hiroshi Kobayashi, Shogo Imanaka.

  The efficacy of assisted reproductive technologies (ARTs) in older women remains constrained, largely due to an incomplete understanding of the underlying pathophysiology. This review aims to consolidate the current knowledge on age-associated mitochondrial alterations and their implications for ovarian aging, with an emphasis on the causes of mitochondrial DNA (mtDNA) mutations, their repair mechanisms, and future therapeutic directions. Relevant articles published up to 30 September 2024 were identified through a systematic search of electronic databases. The free radical theory proposes that reactive oxygen species (ROS) inflict damage on mtDNA and impair mitochondrial function essential for ATP generation in oocytes. Oocytes face prolonged pressure to repair mtDNA mutations, persisting for up to five decades. MtDNA exhibits limited capacity for double-strand break repair, heavily depending on poly ADP-ribose polymerase 1 (PARP1)-mediated repair of single-strand breaks. This process depletes nicotinamide adenine dinucleotide (NAD⁺) and ATP, creating a detrimental cycle where continued mtDNA repair further compromises oocyte functionality. Interventions that interrupt this destructive cycle may offer preventive benefits. In conclusion, the cumulative burden of mtDNA mutations and repair demands can lead to ATP depletion and elevate the risk of aneuploidy, ultimately contributing to ART failure in older women.

Keywords:  aging oocytes; mitochondrial DNA (mtDNA); mtDNA mutations; nicotinamide adenine dinucleotide; poly ADP-ribose polymerase 1 (PARP1)

DOI:  https://doi.org/10.3390/ijms252313144
Postep Psychiatr Neurol. 2024 Sep;33(3): 147-162

Secretome - the role of extracellular vesicles in the pathogenesis and therapy of neurodegenerative diseases.

Anna Sulek.

   Purpose: Extracellular vesicles are the subject of many studies in various medical specialties. Their role in neurodegenerative diseases is increasing and they worth introducing in more detail.
Methods: This review was performed following an electronic search of the database PubMed/Medline and Web of Science for English-language articles between 2010 and 2024 in the fields of medicine, molecular biology, and biochemistry. Keywords searches included combinations of the following terms: "extracellular vesicles" OR "exosomes" AND "neurodeg*" AND "microRNA" OR "miRNA" AND "AD" OR "PD" OR "ALS" OR "HD". Articles had to be original work or reviews.
Results: The classification of extracellular vesicles is based on their size or origin. Their content is of key importance in communication between cells and can be treated as a physiological determinant of the normal or pathological condition of a body. The cargo transported in the extracellular space and over longer distances in various body fluids is diversified and may be nucleic acids (DNA, RNA, miRNA) as well as proteins and lipids, and, in the case of apoptotic bodies also a cell's organelles. Exosomes are the most thoroughly studied extracellular vesicles and the most often considered for therapeutic applications. Vesicles carrying biological substances in the body perform three basic functions: participation in a pathological mechanism, a biomarker role that also has diagnostic and prognostic functions, and a role in therapeutic activities. In the case of neurodegenerative diseases, it appears that extracellular vesicles can transport misfolded proteins, initiating pathological processes in previously normal cells.
Conclusions: The transport of various substances enclosed in vesicles seems to be very promising in therapeutic prospects in various diseases, and the possibility of their crossing the blood-brain barrier particularly indicates diseases of the central nervous system. Despite many years of research on extracellular vesicles in the context of neurodegenerative diseases, their practical use is currently limited to studies on animal and cellular models, and their practical application in clinical trials in neurodegenerative diseases is to date extremely rare.

Keywords:  exosomes; extracellular transport; extracellular vesicles; neurodegenerative disorders; secretome

DOI:  https://doi.org/10.5114/ppn.2024.144686
Front Immunol. 2024 ;15 1440313

The antioxidant barrier, oxidative/nitrosative stress, and protein glycation in allergy: from basic research to clinical practice.

Grzegorz Biedrzycki, Blanka Wolszczak-Biedrzycka, Justyna Dorf, Mateusz Maciejczyk.

  Recent studies indicate that oxidative/nitrosative stress is involved in the pathogenesis of asthma, allergic rhinitis, atopic dermatitis, and urticaria. The article aimed to review the latest literature on disruptions in redox homeostasis and protein glycation in allergy patients. It has been shown that enzymatic and non-enzymatic antioxidant systems are impaired in allergic conditions, which increases cell susceptibility to oxidative damage. Reactive oxygen/nitrogen species exacerbate the severity of asthma symptoms by activating inflammatory mediators that cause airway smooth muscle contraction, promote mucus hypersecretion, increase the permeability of lung capillaries, and damage cell membranes. Redox biomarkers could have considerable diagnostic potential in allergy patients. There is no compelling evidence to indicate that antioxidants reduce allergy symptoms' severity or slow disease progression.

Keywords:  allergy; antioxidants; nitrosative stress; oxidative stress; protein glycation

DOI:  https://doi.org/10.3389/fimmu.2024.1440313