Caloric restriction: A potential approach for mitigating neuronal damage: Lesson from cellular model of Alzheimer disease DOI Creative Commons
Apoorv Sharma,

Monika Bhardwaj,

Vijay Kumar

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

Abstract Alzheimer’s disease is a neurodegenerative disorder and characterized by amyloid beta accumulation, synaptic dysfunction, oxidative stress, lacks effective therapies. Caloric restriction mimetics such as fisetin chlorogenic acid, natural polyphenols with antioxidant autophagy-inducing properties, show promise in mitigating age-related diseases. This study investigates their neuroprotective effects against induced toxicity differentiated human neuroblastoma SHSY5Y cells. Amyloid exposure disrupted redox homeostasis, impaired autophagy, mitochondrial exacerbating neuronal degeneration. Fisetin acid treatments reversed these deleterious restoring balance, suppressing reactive oxygen species upregulating critical enzymes like SOD1, GSR, catalase. These compounds also attenuated mitophagy via reduced PINK1 expression restored fusion Mfn2. Autophagy-related pathways were significantly modulated, evidenced increased AMPK decreased mTOR mRNA levels, alongside elevated of ATG101, ATG13, ULK1, P62 ATG5 levels. Docking studies revealed binding CGA within the pockets FKBP12 supporting interaction. Furthermore, improved integrity PSD95 synaptophysin reducing acetylcholinesterase expression. findings highlight potential ameliorating through autophagy activation, preservation, function enhancement. While this demonstrates transcriptional impact affinities caloric further translational biophysical analyses are required to elucidate mechanisms confirm therapeutic viability. research underscores agents, offering promising avenues for combating related neuropathies. Figure

Language: Английский

Caloric restriction: A potential approach for mitigating neuronal damage: Lesson from cellular model of Alzheimer disease DOI Creative Commons
Apoorv Sharma,

Monika Bhardwaj,

Vijay Kumar

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

Abstract Alzheimer’s disease is a neurodegenerative disorder and characterized by amyloid beta accumulation, synaptic dysfunction, oxidative stress, lacks effective therapies. Caloric restriction mimetics such as fisetin chlorogenic acid, natural polyphenols with antioxidant autophagy-inducing properties, show promise in mitigating age-related diseases. This study investigates their neuroprotective effects against induced toxicity differentiated human neuroblastoma SHSY5Y cells. Amyloid exposure disrupted redox homeostasis, impaired autophagy, mitochondrial exacerbating neuronal degeneration. Fisetin acid treatments reversed these deleterious restoring balance, suppressing reactive oxygen species upregulating critical enzymes like SOD1, GSR, catalase. These compounds also attenuated mitophagy via reduced PINK1 expression restored fusion Mfn2. Autophagy-related pathways were significantly modulated, evidenced increased AMPK decreased mTOR mRNA levels, alongside elevated of ATG101, ATG13, ULK1, P62 ATG5 levels. Docking studies revealed binding CGA within the pockets FKBP12 supporting interaction. Furthermore, improved integrity PSD95 synaptophysin reducing acetylcholinesterase expression. findings highlight potential ameliorating through autophagy activation, preservation, function enhancement. While this demonstrates transcriptional impact affinities caloric further translational biophysical analyses are required to elucidate mechanisms confirm therapeutic viability. research underscores agents, offering promising avenues for combating related neuropathies. Figure

Language: Английский

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