bims-metalz 2024-03-03 papers

Issue of 2024–03–03
two papers selected by
Mikaila Chetty, Goa University

Exp Brain Res. 2024 Mar 02.

Autophagy and UPS pathway contribute to nicotine-induced protection effect in Parkinson's disease.

Inam Ullah, Shahab Uddin, Longhe Zhao, Xin Wang, Hongyu Li.

The gradual nature of age-related neurodegeneration causes Parkinson's disease (PD) and impairs movement, memory, intellectual ability, and social interaction. One of the most prevalent neurodegenerative conditions affecting the central nervous system (CNS) among the elderly is PD. PD affects both motor and cognitive functions. Degeneration of dopaminergic (DA) neurons and buildup of the protein α-synuclein (α-Syn) in the substantia nigra pars compacta (SNpc) are two major causes of this disorder. Both UPS and ALS systems serve to eliminate α-Syn. Autophagy and UPS deficits, shortened life duration, and lipofuscin buildup accelerate PD. This sickness has no cure. Innovative therapies are halting PD progression. Bioactive phytochemicals may provide older individuals with a natural substitute to help delay the onset of neurodegenerative illnesses. This study examines whether nicotine helps transgenic C. elegans PD models. According to numerous studies, nicotine enhances synaptic plasticity and dopaminergic neuronal survival. Upgrades UPS pathways, increases autophagy, and decreases oxidative stress and mitochondrial dysfunction. At 100, 150, and 200 µM nicotine levels, worms showed reduced α-Syn aggregation, repaired DA neurotoxicity after 6-OHDA intoxication, increased lifetime, and reduced lipofuscin accumulation. Furthermore, nicotine triggered autophagy and UPS. We revealed nicotine's potential as a UPS and autophagy activator to prevent PD and other neurodegenerative diseases.

Keywords: Caenorhabditis elegans ; Autophagy; Lgg-1; Longevity; Nicotine; Parkinson’s disease; Proteasome (UPS); α-Synuclein

DOI: https://doi.org/10.1007/s00221-023-06765-9

Arch Gerontol Geriatr. 2024 Feb 20. pii: S0167-4943(24)00053-0. [Epub ahead of print]122 105377

Cynaroside extends lifespan and improves the neurondegeneration diseases via insulin/IGF-1 signaling pathway in Caenorhabditis elegans.

Yi Xiao, Yan Zhang, Linlu Li, Nian Jiang, Changyan Yu, Sanhua Li, Xinting Zhu, Fang Liu, Yun Liu.

The evolutionarily conserved insulin/IGF-1 signaling pathway plays a central role in aging and aging related diseases such as neurodegeneration diseases. Inhibition of insulin/IGF-1 signaling pathway has been proposed as an effective way to extend lifespan and delay neurodegeneration diseases in different organisms. Cynaroside (Cyn), a flavonoid contained in many medical plants and in vegetables, had been shown to exhibit pharmacological properties such as anti-inflammatory, anti-tumor, and anti-oxidant effects. The study demonstrated that lifespan extension and neurodegeneration diseases improving could be achieved by targeting evolutionarily conserved insulin/IGF-1 pathway through using pharmacological interventions. Via using this approach in tractable model Caenorhabditis elegans, we found that 10 μM Cynaroside significantly promoted the healthy lifespan in wild-type animals. Furthermore, via genetic screen, we showed that Cynaroside acted on IGF-1-R /DAF-2, which was followed by the activation of transcription factor DAF-16/FOXO to extend the healthy lifespan. Intriguingly, Cynaroside also improved neurodegeneration diseases such as Alzheimer's and polyglutamine disease by suppressing insulin/IGF-1 signaling pathway. Our work suggests that Cynaroside may be a promising candidate for the prevention and treatment of aging and neurodegeneration diseases.

Keywords: Caenorhabditis elegans; Cynaroside; Insulin/IGF-1 signaling pathway; Lifespan; Neurodegeneration diseases

DOI: https://doi.org/10.1016/j.archger.2024.105377