Selective neuronal vulnerability in Parkinson disease

Nature reviews. Neuroscience, Год журнала: 2017, Номер 18(2), С. 101 - 113

Опубликована: Янв. 20, 2017

Язык: Английский

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Microglia monitor and protect neuronal function through specialized somatic purinergic junctions

Science, Год журнала: 2019, Номер 367(6477), С. 528 - 537

Опубликована: Дек. 13, 2019

Microglia are the main immune cells in brain and have roles homeostasis neurological diseases. Mechanisms underlying microglia-neuron communication remain elusive. Here, we identified an interaction site between neuronal cell bodies microglial processes mouse human brain. Somatic junctions a specialized nanoarchitecture optimized for purinergic signaling. Activity of mitochondria was linked with junction formation, which induced rapidly response to activation blocked by inhibition P2Y12 receptors. Brain injury-induced changes at somatic triggered receptor-dependent neuroprotection, regulating calcium load functional connectivity. Thus, these could potentially monitor protect functions.

Язык: Английский

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Mitochondrial dynamics in health and disease: mechanisms and potential targets

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Сен. 6, 2023

Abstract Mitochondria are organelles that able to adjust and respond different stressors metabolic needs within a cell, showcasing their plasticity dynamic nature. These abilities allow them effectively coordinate various cellular functions. Mitochondrial dynamics refers the changing process of fission, fusion, mitophagy transport, which is crucial for optimal function in signal transduction metabolism. An imbalance mitochondrial can disrupt function, leading abnormal fate, range diseases, including neurodegenerative disorders, cardiovascular diseases cancers. Herein, we review mechanism dynamics, its impacts on function. We also delve into changes occur during health disease, offer novel perspectives how target modulation dynamics.

Язык: Английский

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PINK1 and Parkin mitochondrial quality control: a source of regional vulnerability in Parkinson’s disease

Molecular Neurodegeneration, Год журнала: 2020, Номер 15(1)

Опубликована: Март 13, 2020

Abstract That certain cell types in the central nervous system are more likely to undergo neurodegeneration Parkinson’s disease is a widely appreciated but poorly understood phenomenon. Many vulnerable subpopulations, including dopamine neurons substantia nigra pars compacta, have shared phenotype of large, distributed axonal networks, dense synaptic connections, and high basal levels neural activity. These features come at substantial bioenergetic cost, suggesting that these experience degree mitochondrial stress. In such context, mechanisms quality control play an especially important role maintaining neuronal survival. this review, we focus on understanding unique challenges faced by mitochondria summarize evidence dysfunction contributes pathogenesis death subpopulations. We then review mediated activation PINK1 Parkin, two genes carry mutations associated with autosomal recessive disease. conclude pinpointing critical gaps our knowledge Parkin function, propose connection between sporadic defects will lead us greater insights into question selective vulnerability.

Язык: Английский

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Mitochondria and Reactive Oxygen Species in Aging and Age-Related Diseases

International review of cell and molecular biology, Год журнала: 2018, Номер unknown, С. 209 - 344

Опубликована: Янв. 1, 2018

Язык: Английский

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The different autophagy degradation pathways and neurodegeneration

Neuron, Год журнала: 2022, Номер 110(6), С. 935 - 966

Опубликована: Фев. 7, 2022

Язык: Английский

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Axonal transport: Driving synaptic function

Science, Год журнала: 2019, Номер 366(6462)

Опубликована: Окт. 11, 2019

From trafficking to maintenance Neurons are remarkably polarized in that proteins made the cytosol often need travel many tens or hundreds of cell body lengths along axons their sites action synapse. Axonal transport these components is driven by molecular motors axonal microtubules. Guedes-Dias and Holzbaur review biology highlight roles this fundamental process plays organismal health. Science , issue p. eaaw9997

Язык: Английский

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Cell-type-specific profiling of brain mitochondria reveals functional and molecular diversity

Nature Neuroscience, Год журнала: 2019, Номер 22(10), С. 1731 - 1742

Опубликована: Сен. 9, 2019

Язык: Английский

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Mitochondria-lysosome contacts regulate mitochondrial Ca ²⁺ dynamics via lysosomal TRPML1

Proceedings of the National Academy of Sciences, Год журнала: 2020, Номер 117(32), С. 19266 - 19275

Опубликована: Июль 23, 2020

Significance Mitochondria and lysosomes are critical for cellular homeostasis defects in both organelles observed several diseases. Recently, contact sites between mitochondria were identified found to modulate mitochondrial dynamics. However, whether mitochondria–lysosome contacts have additional functions is unknown. Here, we identify a function of facilitating the direct transfer calcium from mitochondria. Transfer at mediated by lysosomal channel TRPML1 disrupted mucolipidosis type IV, storage disorder caused loss-of-function mutations TRPML1. Calcium thus presents an mechanism intracellular regulation that may further contribute various disorders.

Язык: Английский

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Mitochondrial Dysfunction in Parkinson’s Disease—Cause or Consequence?

Biology, Год журнала: 2019, Номер 8(2), С. 38 - 38

Опубликована: Май 11, 2019

James Parkinson first described the motor symptoms of disease that took his name over 200 years ago. While our knowledge many changes occur in this condition has increased, it is still unknown what causes neurodegeneration and why only affects some individuals with advancing age. Here we review current literature to discuss whether mitochondrial dysfunction have detected Parkinson’s a pathogenic cause neuronal loss or itself consequence other pathways. We examine research data from cases idiopathic model systems familial forms disease. Furthermore, include healthy aged highlight are also present age, though not normally presence severe neurodegeneration. definitive answer question may be just out reach, clear sits prominently at centre pathway leads catastrophic those affected by

Язык: Английский

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