Cited by 603Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsAmyotrophic Lateral Sclerosis Research

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Selective vulnerability in neurodegenerative diseases

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Fu, Hongjun, Hardy, John, Duff, Karen E.·2018·Nature Neuroscience

DOI 10.1038/s41593-018-0221-2PMC PMC6360529

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Abstract

Neurodegenerative diseases have two general characteristics that are so fundamental we usually take them for granted. The first is that the pathology associated with the disease only affects particular neurons ('selective neuronal vulnerability'); the second is that the pathology worsens with time and impacts more regions in a stereotypical and predictable fashion. The mechanisms underpinning selective neuronal and regional vulnerability have been difficult to dissect, but the recent application of whole-genome technologies, the development of mouse models that reproduce spatial and temporal features of the pathology, and the identification of intrinsic morphological, electrophysiological, and biochemical properties of vulnerable neurons are beginning to shed some light on these fundamental features of neurodegenerative diseases. Here we detail our emerging understanding of the underlying biology of selective neuronal vulnerability and outline some of the areas in which our understanding is incomplete.

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Authors: Fu, H., Hardy, J., & Duff, K. E.
Affiliations: Columbia University Irving Medical Center (US)
UCL Queen Square Institute of Neurology (GB)
Corresponding author: Duff, Karen E.
ORCID: Fu, Hongjun
Hardy, John
Duff, Karen E.
Venue: Nature Neuroscience
Publisher: Springer Science and Business Media LLC
Published: 2018-09-24
Volume: 21
Issue: 10
Pages: 1350-1358
ISSN: 1097-6256 (ISSN-L)
1546-1726
DOI: 10.1038/s41593-018-0221-2
PMC: PMC6360529
OpenAlex: W2890004445
Cited by: 585
References: 154
Citations by year: 2026: 87 · 2025: 78 · 2024: 85 · 2023: 67 · 2022: 83 · 2021: 82 · 2020: 60 · 2019: 39 · 2018: 3
FWCI: 6.05
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Neuroscience (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
UCL Discovery (University College London) (submittedVersion)
Funders: National Institute on Aging (RF1AG056151, K01AG056673)
National Institute of Neurological Disorders and Stroke (R01NS074874)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Clinical Neurology › Amyotrophic Lateral Sclerosis Research
Keywords: neurodegenerative diseases, selective neuronal vulnerability, regional vulnerability, disease progression
MeSH terms: Animals, Humans, Neurons, Neurodegenerative Diseases, Genome-Wide Association Study

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