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Neurodegeneration in Familal Amyloidotic Polyneuropathy


Gasperini, RJ and Small, DH, Neurodegeneration in Familal Amyloidotic Polyneuropathy, Clinical and Experimental Pharmacology and Physiology, 39, (8) pp. 680-683. ISSN 0305-1870 (2012) [Refereed Article]

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Copyright 2011 The Authors, Clinical and Experimental Pharmacology and Physiology and Blackwell Publishing Asia Pty Ltd

DOI: doi:10.1111/j.1440-1681.2011.05607.x


1. Familial amyloid polyneuropathies (FAP) constitute a group of inherited amyloidoses that affect peripheral nerves. One common form of FAP is caused by transthyretin (TTR) misfolding and deposition in the peripheral nervous system, leading to neuronal toxicity and death.

2. The molecular mechanisms responsible for this toxicity are unclear, however there is good biochemical and histopathological evidence that the toxicity of TTR mutations is correlated to their aggregation state. In addittion, neuronal calcium dysregulation is a mechanism that has been suggested to drive the pathogenesis of FAP.

3. Amyloidogenic TTR mutations cause significant calcium influx via L-type calcium channels in neuronal cell lines, while in primary sensory neurons, TTR mediates a calcium influx via a novel mechanism of transient receptor potential melanostatin (TRPM8) and voltage-gated sodium and calcium channel activation.

4. Significantly, calcium dysregulation is a pathological hallmark of other neurodegenerative diseases involving amyloidosis, for example Alzheimer's disease, and this mechanism could explain the molecular events that drive amyloid toxicity in other neurodegenerative diseases.

Item Details

Item Type:Refereed Article
Keywords:amyloid, calcium, transthyretin, TRPM8 channels
Research Division:Biomedical and Clinical Sciences
Research Group:Neurosciences
Research Field:Neurosciences not elsewhere classified
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Gasperini, RJ (Dr Rob Gasperini)
UTAS Author:Small, DH (Professor David Small)
ID Code:76286
Year Published:2012 (online first 2011)
Web of Science® Times Cited:5
Deposited By:Menzies Institute for Medical Research
Deposited On:2012-03-03
Last Modified:2017-11-06

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