Early synaptic pathophysiology in neurodegeneration: insights from Huntington's disease

Investigations of synaptic transmission and plasticity in mouse models of Huntington's disease (HD) demonstrate neuronal dysfunction long before the onset of classical disease indicators. Similarly, recent human studies reveal synaptic dysfunction decades before predicted clinical diagnosis in...

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Bibliographic Details
Published in:Trends in neurosciences (Regular ed.) 2010-11, Vol.33 (11), p.513-523
Main Authors: Milnerwood, Austen J, Raymond, Lynn A
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Brain
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Fundamental and applied biological sciences. Psychology
General aspects. Models. Methods
Genes
Genotype & phenotype
Humans
Huntington Disease - physiopathology
Huntingtons disease
Medical sciences
Mice
Mutation
Nerve Degeneration - physiopathology
Neurodegeneration
Neurology
Neuronal Plasticity - physiology
Neurotransmitters
Rodents
Signal transduction
Studies
Synapses - metabolism
Synapses - pathology
Synaptic Transmission - physiology
Vertebrates: nervous system and sense organs
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Summary:Investigations of synaptic transmission and plasticity in mouse models of Huntington's disease (HD) demonstrate neuronal dysfunction long before the onset of classical disease indicators. Similarly, recent human studies reveal synaptic dysfunction decades before predicted clinical diagnosis in HD gene carriers. These studies guide premanifest tracking of disease and the development of treatment assessment tools. New discoveries of mechanisms underlying early neuronal dysfunction, including elevated pathogenic extrasynaptic NMDA receptor signaling, reduced synaptic connectivity and loss of brain-derived neurotrophic factor (BDNF) support have led to pharmacological interventions that can reverse or delay phenotype onset and disease progression in HD mice. Further understanding the primary effects of gene mutations associated with late-onset neurodegeneration should translate to novel treatments for HD families and guide therapeutic strategies for other neurodegenerative diseases.
ISSN:0166-2236
1878-108X
DOI:10.1016/j.tins.2010.08.002