26: Neurodegenerative Disorders Flashcards
Two things aggregates of misfolded proteins cause
- Gain of toxicity
2. Loss of biological function
Neurodegenerative diseases
Large group of neurological disorders primarily affecting neurons, with heterogeneous clinical and pathological expression
Common denominator of neurodegenerative disorders
Misfolded proteins
Familial vs sporadic neurodegenerative disorders
Familial: mutations in specific genes; early onset forms of disease
Sporadic: usually due to brain aging/random mutation; represent late onset of disease
Most common neurodegenerative disorder + most common form of dementia
Alzheimer’s
Extracellular vs intracellular deposits in Alzheimer’s
Extracellular: AB misfolding -> insoluble plaques in the brain
Intracellular: tau proteins are hyperphosphorylated -> form neurofibrillary tangles
Treatment for Parkinson’s
Symptomatic treatment; dopamine replacement therapy, deep brain stimulation, surgery
Role of Htt protein
Development of brain neurons before birth, signaling, transport, protecting cell from apoptosis, possible role in DNA repair
HTT gene normal amount of trinucleotide repeats
10-35 CAG repeats is normal
What does CAG code for? What does it form?
CAG = glutamine; with lots of repeats, the polyglutamine structure forms intramolecular H bonds -> misfolding and aggregation