week 2- protein misfolding Flashcards
differentiate between the proteins misfolded in alzhemiers, huntington, parkinson and prion disease
differentiate dementia and movement disorders
neurodegeneration of the cortex versus the brainstem and basal ganglia
differentiate between the halmark lesions in alzhemiers, huntington, parkinson and prion disease
what is deposited extracellular versus the intracellular in AD and how does one develop versus the other
extracellular- AB, cleavage of APP by B and y secretases
intracellular- tau, hyperphosphorylation misfolding
what are the forms of prion disease
Outline the clinical presentation
converted into abnormal β-pleated conformation
•Sporadic –> CJD(Creutzfeldt-Jakob disease)
•Inherited–> GSS(Gerstmann-Straüssler-Scheinkersyndrome),FFI (Fatal familial insomnia),familial CJD
•Transmitted –> BSE(bovine spongiform encephalopathy) or CJD
•Intracellular vacuoles and neuronal cell death give “spongy” appearance
•Presents as rapidly progressive dementia with ataxia and startle myoclonus
what are the hallmark clinical features of parkinsons
what are the protein inclusions seen?
TRAP =
Tremors (esp. “pill rolling” tremor at rest, disappears with movement)
Rigidity
Akinesia/bradykinesia (slowing of voluntary movements)
Postural instability and shuffling gait; dementia develops late in the disease
•Protein inclusions = intracytoplasmic Lewy bodies of alpha-synuclein
what is the cause of HD
Degeneration of GABAergic neurons in the caudate nucleus of the basal ganglia, with both intranuclear and intracytoplasmic protein inclusions
purely GENETIC!
Autosomal dominant inheritance of expanded trinucleotide repeats (CAG) in huntingtin gene àpolyglutamine tracts in huntingtin protein
what is the clinical presentation of HD
chorea (abnormal involuntary movement), behavioral disturbance, and executive impairment
also:Depression, apathy, social withdrawal, irritability, intermittent disinhibition, delusions, and obsessive-compulsive behavior are common
