Key genes and convergent pathogenic mechanisms in Parkinson disease

Nature reviews. Neuroscience, Journal Year: 2024, Volume and Issue: 25(6), P. 393 - 413

Published: April 10, 2024

Language: Английский

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Stay in touch with the endoplasmic reticulum

Science China Life Sciences, Journal Year: 2024, Volume and Issue: 67(2), P. 230 - 257

Published: Jan. 4, 2024

Language: Английский

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Gaucher disease provides a unique window into Parkinson disease pathogenesis

Nature Reviews Neurology, Journal Year: 2024, Volume and Issue: 20(9), P. 526 - 540

Published: Aug. 6, 2024

Language: Английский

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VPS13C regulates phospho-Rab10-mediated lysosomal function in human dopaminergic neurons

The Journal of Cell Biology, Journal Year: 2024, Volume and Issue: 223(5)

Published: Feb. 15, 2024

Loss-of-function mutations in VPS13C are linked to early-onset Parkinson’s disease (PD). While has been previously studied non-neuronal cells, the neuronal role of disease-relevant human dopaminergic neurons not elucidated. Using live-cell microscopy, we investigated regulating lysosomal dynamics and function iPSC-derived neurons. Loss disrupts morphology with increased inter-lysosomal contacts, leading impaired motility cellular distribution, as well defective hydrolytic activity acidification. We identified Rab10 a phospho-dependent interactor on lysosomes observed decreased phospho-Rab10-mediated stress response upon loss VPS13C. These findings highlight an important homeostasis suggest that disruptions Rab10-mediated contribute pathogenesis VPS13C-linked PD.

Language: Английский

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The Sentient Cell

Oxford University Press eBooks, Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 5, 2023

Abstract This volume is the natural follow-up to Arthur Reber’s 2019 book, The First Minds: Caterpillars, ‘Karyotes, and Consciousness (TFM). In that earlier work, Cellular Basis of (CBC) theory was developed based on a number efforts published in variety journals between 1997 as well talks, colloquia, presentations at conferences. core proposition TFM life mind are co-terminous. All organisms, all species extant extinct, sentient. have an existentially secure consciousness—without which they would been evolutionary dead-ends, unable survive chaotic, dangerous environment first appeared. And, importantly, forms sentience, cognitive functioning right up including those expressed by humans, evolved from original expression consciousness birth prokaryotes. unicellular widely accepted, foundational principle biological social sciences. CBC simply applies same sentience.

Language: Английский

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Neuronal endoplasmic reticulum architecture and roles in axonal physiology

Molecular and Cellular Neuroscience, Journal Year: 2023, Volume and Issue: 125, P. 103822 - 103822

Published: Feb. 11, 2023

The endoplasmic reticulum (ER) is the largest membrane compartment within eukaryotic cells and emerging as a key coordinator of many cellular processes. ER can modulate local calcium fluxes communicate with other organelles like plasma membrane. importance in neuronal processes such neurite growth, axon repair neurotransmission has recently gained much attention. In this review, we highlight tubular network axonal homeostasis discuss how generation maintenance thin axons synapses, requires cooperative effort ER-shaping proteins, cytoskeleton autophagy

Language: Английский

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The Endoplasmic Reticulum and Its Contacts: Emerging Roles in Axon Development, Neurotransmission, and Degeneration

The Neuroscientist, Journal Year: 2023, Volume and Issue: 30(5), P. 545 - 559

Published: March 24, 2023

The neuronal endoplasmic reticulum (ER) consists of a dynamic, tubular network that extends all the way from soma into dendrites, axons, and synapses. This morphology gives rise to an enormous membrane surface area that, through presence tethering proteins, lipid transfer ion channels, plays critical roles in local calcium regulation, dynamics, supply ions lipids other organelles. Here, we summarize recent advances highlight various ER axonal growth, repair, presynaptic function. We review variety contact sites between organelles describe their influence on neurodevelopment neurotransmission.

Language: Английский

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IP₃R at ER-Mitochondrial Contact Sites: Beyond the IP₃R-GRP75-VDAC1 Ca²⁺ Funnel

Contact, Journal Year: 2023, Volume and Issue: 6

Published: Jan. 1, 2023

Membrane contact sites (MCS) circumvent the topological constraints of functional coupling between different membrane-bound organelles by providing a means communication and exchange materials. One most characterised in cell is that endoplasmic reticulum mitochondrial (ERMCS) whose function to couple cellular Ca

Language: Английский

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Misregulation of mitochondria–lysosome contact dynamics in Charcot–Marie–Tooth Type 2B disease Rab7 mutant sensory peripheral neurons

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(44)

Published: Oct. 25, 2023

Inter-organelle contact sites between mitochondria and lysosomes mediate the crosstalk bidirectional regulation of their dynamics in health disease. However, mitochondria–lysosome misregulation have not been investigated peripheral sensory neurons. Charcot–Marie–Tooth type 2B disease is an autosomal dominant axonal neuropathy affecting neurons caused by mutations GTPase Rab7. Using live super-resolution confocal time-lapse microscopy, we showed that dynamically form soma axons Interestingly, mutant Rab7 led to prolonged site tethering preferentially neurons, due impaired GTP hydrolysis–mediated untethering. We further generated a knock-in mouse model which exhibited defective downstream mitochondrial hydrolysis as well fragmented axon sciatic nerve. Importantly, mice demonstrated preferential behavioral abnormalities neuropathy, highlighting important role for driving degeneration Together, this study identifies pathogenesis neuropathy.

Language: Английский

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Multi-organelle-mediated mRNA localization in neurons and links to disease

Current Opinion in Genetics & Development, Journal Year: 2025, Volume and Issue: 92, P. 102332 - 102332

Published: March 7, 2025

Brain function requires precise spatiotemporal regulation of the neuronal proteome. To allow adaptation proteome in distal outposts neurons, mRNAs are transported into neurites for localized translation. This mRNA localization and local translation is crucial neuron maintenance, dysregulation these processes can contribute to neurological disease. Recently, organelles have emerged as key players regulating dendrites axons. In this review, we discuss current evidence open questions organelle-mediated localization. We highlight an emerging model which multiple create orchestrate a subcellular microenvironment that support selective seems essential maintaining organellar health, mutations many involved proteins lead various disorders.

Language: Английский

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