The molecular basis of some neurodegenerative diseases Flashcards
what is genetic anticipation
for familial diseases, the disease onset become earlier with each generation and the symptoms become more severe. Found in neurological diseases with common in trinucleotide repeats
name some trinucleotide repeat disorders
fragile X huntingtons spinobulbar muscular atrophy spinocerebellar ataxia myotonic dystrophy
what parts of the brain are most affected in huntingtons
striatum
caudate and putamen
what is the genetic repeat in huntingtons
CAG, which codes for glutamine, hence a polyglutamine tract in the coding region causes an altered protein
what is the effect of polyglutamine tracts in Huntington gene
protein misfolds and aggregates, creating inclusion bodies
what are the features of fragile X
mild to moderate learning disability
single gene disorder on X chromosome
males twice as likely as females (x linked dominant)
Long face - prominent forehead & jaw
Mitral valve prolapse
ADD
autistic like behaviours
what are the inheritance features of fragile X
FMR1 CGG repeat trinucleotide expansion involves 'premutations' found in non coding region transcriptional silencing (down regulation of a gene)
describe the FMR1 protein
highly expressed in neurons
regulates mRNA translation in dendrites
what are the features of myotonic dystrophy
gradually worsening muscle loss and weakness. Muscles often contract and are unable to relax. cataracts, intellectual disability, heart conduction problems. autosomal dominant
displays genetic anticipation (classical and congenital forms, depending on number of repeats)
describe the implications of amyloid precursor protein in alzeimers
abnormal cleavage of amyloid precursor protein leads to excess amyloid accumulation
what disease are presenilin 1 and 2 associated with
early onset Alzheimer’s disease
affects gamma secretase enzyme complex
what is the function of apolipoprotein E
cholesterol transport and clears amyloid B
break down might generate toxic products
what possible treatments could be used for alzeimer’s in the future
secretatse inhibitors prevents phosphorylation of tau aggregation inhibitors statins immunisation
name some prion diseases (transmissible spongiform encephalopathy)
creutzfeld jakob disease
kuru
fatal familial insomnia
may be inherited, sporadic or acquired
what is variant CJD
CJD from eating infected beef
