Ageing Neurodegeneration Flashcards
pathology of Huntington’s disease
exact function of normal Huntington protein is poorly defined. thought to be the accumulation of the abnormal protein is what causes the neurological changes. with the excess protein interfering with neurotransmitters
is Huntington disease autosomal dominant
yes
where do errors occur in the Huntington disease gene
expansions of the 23 Q / GLUTAMINE - repeat region past 197 to 265 nucleotide sequence on amino acids 18 to 40.
pathological changes with expansion of polyglutamine repeat
unstable polyglutamien repeat in protein product. causing impairment of the ubiquitin-proteasome system. and the dysfunctional protein is not removed and extorted as it otherwise should be.
what are the symptoms of Huntington disease
cognitive / amnesia muscular / spasms behavioural / fidgeting psychological / hallucination mood / anxiety
examples of each
what happens to an aged CNS
brain and spinal chord lose nerve endings and show atrophy
neuronal function decline with decreased rate of condition and increased synapse time. slowing the processes of thought and memory
cellular changes in ageing CNS
lipofuscin deposits within nerve tissue
decrease in nil bodies - responsible for the synthesis of proteins in the neuronal cytoplasm.
glial numbers tend to increase to that 10 times to that of neurones
what is Alzheimers disease
neruodegenrative disease causing progressive memory and language loss. associated with deposites of APP protein and neurofibrillary tangles. NFTS being clumps of tau protein.
shrinkage of the hippocampus and cortical areas can also be seen
how do plaques form in Alzheimers
amyloid protein (APP) extends and wafts on the surface of the membrane. enzymes come and cut and have a function then locally or distally. cut protein is called a beta amyloid protein. these are sticky and the fragments cling together along with other material outside the cell - forming the plaques seen
pathogenesis of Alzheimers.
the accumulation of beta amyloid plaques initiates a series of ‘events’. triggering neuronal cell death and an inflammatory response. with the clumping of tau protein leading to NFTs being caused from beta amyloid production and clearances imbalances
leading to progressive decline in cognitive function and eventual cell death.
the accumulation of beta amyloid is determined by production of tau protein/ presenting proteins and production of the peptide its self
with degradation and clearance from the levels of plasmin.
what is PD
progressive neurodegenrative disease caused from the loss fo dopinergic neurones in the substantia nigra. along with the association of Lewy bodies (clubs of alpha synuclein). leading to reduced production of dopamine
what are the symptoms of PD
involuntary tremors muscle rigidity bradykinesia and hypokinesia postural instability visual and cognitive problems
what is Lewy bodies disease
mutations in the alpha synculein protein.
how would you prove the effect of dopamine loss in PD
model to recapitulate reduction in dopamine through the provision of a drug for example such as
6-OHDA a neurotransmitter analogue, depleting noradrenergic store in nerve endings
masliah et all 2000
