Protein Phase Separation: A New Phase in Cell Biology

Trends in Cell Biology, Год журнала: 2018, Номер 28(6), С. 420 - 435

Опубликована: Март 27, 2018

Язык: Английский

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The proteostasis network and its decline in ageing

Nature Reviews Molecular Cell Biology, Год журнала: 2019, Номер 20(7), С. 421 - 435

Опубликована: Фев. 7, 2019

Язык: Английский

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Spinocerebellar ataxia

Nature Reviews Disease Primers, Год журнала: 2019, Номер 5(1)

Опубликована: Апрель 11, 2019

Язык: Английский

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TDP-43 pathology disrupts nuclear pore complexes and nucleocytoplasmic transport in ALS/FTD

Nature Neuroscience, Год журнала: 2018, Номер 21(2), С. 228 - 239

Опубликована: Янв. 4, 2018

The cytoplasmic mislocalization and aggregation of TAR DNA-binding protein-43 (TDP-43) is a common histopathological hallmark the amyotrophic lateral sclerosis frontotemporal dementia disease spectrum (ALS/FTD). However, composition aggregates their contribution to process remain unknown. Here we used proximity-dependent biotin identification (BioID) interrogate interactome detergent-insoluble TDP-43 found them enriched for components nuclear pore complex nucleocytoplasmic transport machinery. Aggregated disease-linked mutant triggered sequestration and/or nucleoporins factors, interfered with protein import RNA export in mouse primary cortical neurons, human fibroblasts induced pluripotent stem cell-derived neurons. Nuclear pathology present brain tissue cases sporadic ALS those involving genetic mutations TARDBP C9orf72. Our data strongly implicate TDP-43-mediated defects as mechanism ALS/FTD.

Язык: Английский

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Cytoplasmic TDP-43 De-mixing Independent of Stress Granules Drives Inhibition of Nuclear Import, Loss of Nuclear TDP-43, and Cell Death

Neuron, Год журнала: 2019, Номер 102(2), С. 339 - 357.e7

Опубликована: Март 7, 2019

Язык: Английский

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Stress Granule Assembly Disrupts Nucleocytoplasmic Transport

Cell, Год журнала: 2018, Номер 173(4), С. 958 - 971.e17

Опубликована: Апрель 5, 2018

Язык: Английский

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Tau Protein Disrupts Nucleocytoplasmic Transport in Alzheimer’s Disease

Neuron, Год журнала: 2018, Номер 99(5), С. 925 - 940.e7

Опубликована: Сен. 1, 2018

Язык: Английский

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Polyglutamine Repeats in Neurodegenerative Diseases

Annual Review of Pathology Mechanisms of Disease, Год журнала: 2018, Номер 14(1), С. 1 - 27

Опубликована: Авг. 8, 2018

Among the age-dependent protein aggregation disorders, nine neurodegenerative diseases are caused by expansions of CAG repeats encoding polyglutamine (polyQ) tracts. We review clinical, pathological, and biological features these inherited disorders. discuss insights into pathogenesis gleaned from studies model systems patients, highlighting work that informs efforts to develop effective therapies. An important conclusion analyses is expanded CAG/polyQ domains primary drivers neurodegeneration, with biology carrier proteins influencing disease-specific manifestations. Additionally, it has become apparent repeat produce neurodegeneration via multiple downstream mechanisms, involving both gain- loss-of-function effects. This indicates likelihood developing therapies targeting single nodes reduced. The evaluation treatments for premanifest disease will likely require new investigational approaches. highlight opportunities challenges underlying ongoing provide recommendations related development symptomatic disease-modifying biomarkers could inform future research.

Язык: Английский

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Emerging insights into the complex genetics and pathophysiology of amyotrophic lateral sclerosis

The Lancet Neurology, Год журнала: 2022, Номер 21(5), С. 465 - 479

Опубликована: Март 22, 2022

Язык: Английский

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Lost in Transportation: Nucleocytoplasmic Transport Defects in ALS and Other Neurodegenerative Diseases

Neuron, Год журнала: 2017, Номер 96(2), С. 285 - 297

Опубликована: Окт. 1, 2017

Язык: Английский

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