title: The differential susceptibility of specific neuronal populations: insights from Huntington's disease.
abstract: Recent successes in identifying the genes and associated proteins underlying several familial neurodegenerative conditions have not always resulted in accounts as to why the associated patterns of neuronal damage are so specific and limited. Here, with reference to Huntington's disease, we present a general scheme to show how the mutant protein could interact with associated proteins to form an aggregation product. This could lead to neuronal death by direct actions on caspases, or by raising the levels of intracellular calcium ions and reactive oxygen species above a threshold that cannot be resisted by the protection normally conferred by endogenous factors such as calcium binding proteins, free radical scavengers and trophic factors. The local distributions of vulnerability and protective factors could ultimately dictate the pattern of damage induced by the mutant gene.
authors.affiliation: School of Psychology, University of Birmingham, Birmingham, B15 2TT, UK. I.J.Mitchell@bham.ac.uk
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Mitchell
authors.forename: Mark R
authors.initials: MR
authors.lastname: Griffiths
mesh_terms: D016923:Cell Death; D004198:Disease Susceptibility; D005786:Gene Expression Regulation; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D009154:Mutation; D009410:Nerve Degeneration / Q000235:genetics; D009474:Neurons / Q000473:pathology / Q000502:physiology*