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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Hallmarks of neurodegenerative diseases

Cell, Год журнала: 2023, Номер 186(4), С. 693 - 714

Опубликована: Фев. 1, 2023

Summary

Decades of research have identified genetic factors and biochemical pathways involved in neurodegenerative diseases (NDDs). We present evidence for the following eight hallmarks NDD: pathological protein aggregation, synaptic neuronal network dysfunction, aberrant proteostasis, cytoskeletal abnormalities, altered energy homeostasis, DNA RNA defects, inflammation, cell death. describe hallmarks, their biomarkers, interactions as a framework to study NDDs using holistic approach. The can serve basis defining pathogenic mechanisms, categorizing different based on primary stratifying patients within specific NDD, designing multi-targeted, personalized therapies effectively halt NDDs.

Язык: Английский

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Roles of tau protein in health and disease

Acta Neuropathologica, Год журнала: 2017, Номер 133(5), С. 665 - 704

Опубликована: Апрель 6, 2017

Tau is well established as a microtubule-associated protein in neurons. However, under pathological conditions, aberrant assembly of tau into insoluble aggregates accompanied by synaptic dysfunction and neural cell death range neurodegenerative disorders, collectively referred to tauopathies. Recent advances our understanding the multiple functions different locations inside outside neurons have revealed novel insights its importance diverse molecular pathways including signalling, plasticity, regulation genomic stability. The present review describes physiological pathophysiological properties how these relate distribution We highlight post-translational modifications tau, which are pivotal defining modulating localisation roles health disease. include discussion other pathologically relevant changes mutation aggregation, aspects impinge on propensity propagate, potentially drive neuronal loss, diseased brain. Finally, we describe cascade events that may be driven dysfunction, impaired axonal transport, alterations synapse mitochondrial function, activation unfolded response defective degradation. It important fully understand attributed since this will provide vital information involvement development pathogenesis Such knowledge enable determination critical should targeted potential therapeutic agents developed for treatment

Язык: Английский

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ALS Genetics, Mechanisms, and Therapeutics: Where Are We Now?

Frontiers in Neuroscience, Год журнала: 2019, Номер 13

Опубликована: Дек. 6, 2019

The scientific landscape surrounding amyotrophic lateral sclerosis (ALS) continues to shift as the number of genes associated with disease risk and pathogenesis, cellular processes involved, grow. Despite decades intense research over 50 potentially causative or disease-modifying identified, etiology remains unexplained treatment options remain limited for majority ALS patients. Various factors have contributed slow progress in understanding developing therapeutics this disease. Here we review genetic basis ALS, highlighting that elusiveness heritability. most commonly mutated ALS-linked are reviewed an emphasis on disease-causing mechanisms. involved pathogenesis discussed, evidence implicating their involvement summarized. Past present therapeutic strategies benefits limitations model systems available researchers discussed future directions may lead effective outlined.

Язык: Английский

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Axonal Transport: Cargo-Specific Mechanisms of Motility and Regulation

Neuron, Год журнала: 2014, Номер 84(2), С. 292 - 309

Опубликована: Окт. 1, 2014

Язык: Английский

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Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

Neuron, Год журнала: 2018, Номер 97(6), С. 1267 - 1288

Опубликована: Март 1, 2018

Язык: Английский

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Building the Neuronal Microtubule Cytoskeleton

Neuron, Год журнала: 2015, Номер 87(3), С. 492 - 506

Опубликована: Авг. 1, 2015

Язык: Английский

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Development of Multifunctional Molecules as Potential Therapeutic Candidates for Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis in the Last Decade

Chemical Reviews, Год журнала: 2018, Номер 119(2), С. 1221 - 1322

Опубликована: Авг. 10, 2018

Neurodegenerative diseases pose a substantial socioeconomic burden on society. Unfortunately, the aging world population and lack of effective cures foreshadow negative outlook. Although large amount research has been dedicated to elucidating pathologies neurodegenerative diseases, their principal causes remain elusive. Metal ion dyshomeostasis, proteopathy, oxidative stress, neurotransmitter deficiencies are pathological features shared across multiple disorders. In addition, these factors proposed be interrelated upon disease progression. Thus, development multifunctional compounds capable simultaneously interacting with several components suggested as solution undertake complex diseases. this review, we outline discuss possible therapeutic targets in Alzheimer's disease, Parkinson's amyotrophic lateral sclerosis molecules, previously designed or discovered potential drug candidates for disorders emphasis multifunctionality. underrepresented areas discussed indicate new directions.

Язык: Английский

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Mitostasis in Neurons: Maintaining Mitochondria in an Extended Cellular Architecture

Neuron, Год журнала: 2017, Номер 96(3), С. 651 - 666

Опубликована: Ноя. 1, 2017

Язык: Английский

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There's Something Wrong with my MAM; the ER–Mitochondria Axis and Neurodegenerative Diseases

Trends in Neurosciences, Год журнала: 2016, Номер 39(3), С. 146 - 157

Опубликована: Фев. 16, 2016

TrendsMitochondria and the ER form close physical contacts.ER–mitochondria contacts regulate functions damaged in neurodegenerative diseases.ER–mitochondria are diseases.AbstractAlzheimer's disease (AD), Parkinson's (PD), amyotrophic lateral sclerosis with associated frontotemporal dementia (ALS/FTD) major diseases for which there no cures. All characterised by damage to several seemingly disparate cellular processes. The broad nature of this makes understanding pathogenic mechanisms devising new treatments difficult. Can different be linked together a common pathway function should targeted therapy? Many regulated communications that mitochondria make specialised region endoplasmic reticulum (ER; mitochondria-associated membranes or 'MAM'). Moreover, recent studies have shown disturbances ER–mitochondria occur diseases. Here, we review these findings.

Язык: Английский

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