Huntingons Flashcards
describe HD
autosomal dominant neurodegenerative disorder caused by exapdned CAG repeats on chromosome 4 (Htt gene), resulting in aggregate formation of mutant Htt
when is onset of disease usually
35 - 60
3 main symtpoms
decline in cognitive function
behavioural problems
physical impairments
causes a degeneration of ________ and ____-ergic cells in basal ganglia
cholinergic
GABA ergic
what is the hallmark of HD
medium spiny neurons
what are MSNS
also know as spiny projection neurons
they are a special tpy eof GABAergic inhibitory cell that represents 95% of the striatum in the basal ganglia
what is the funciton of MSNs
to coordiante info from other neurons to control movement of body face and eyes
in HD, neurons that project to the ______ ______ degenrate which causes it to becom eunusally active. this lead sto excessive actiation of movement related circuits results in chorea
globus pallidus
what happens to MSNs in HD
large numbers of MSN are destroyed and damaged so thers a loss of coordianting muscle movement
describe what goes wrong in the transcirption on the short arm of chromosome 4
chromosome 4 holds the HD/hTT gene
- transcription usually has less have CAG codes which code for glutamine
- but in HD, CAG repeats ar emore than 36, leading to way too many glutamine in the chain
whats the difference of juvenile HD and adult HD?
adult
- 36-60 repeats
- progressive and predictable
- starts at caudate putamen to cerebral cortex
young
- over 60 repeats
- widespread and variable
what are 6 major molecular issues from HD?
- glutamate excitatoxicity
- autophagy deficits
- less neurotrophic support
- mitochondiral abnormalities
- unabalnced homeostasis of apoptotic molecules
- transcriptional dysregulation
