Parkinsons Flashcards
typical symptoms
-Bradykinesia
-resting tremor
-loss of smell
-sleep dysfunction
-mood disorders
-excess salivation`
2 types of synucleionopathies
with or without Lew Bodies
Synucleinopathies with Lewy bdoies
-Parkinsons disease
-Lewy body disease
Dementia with Lewy Bodies (Lewy body disease) effects
-causes dementia
-feeling less alert and having trouble focusing
-unlike alzeiheimers, it causes specific movement issues
-Visual hallucinations
-sleep problems
early stages
-slowed movement
-muscle stiffness
-tremors
-shuffling walk
late stages
-dementia
Synucleinopathies without lewy bodies
-Multiple systemic atrophy
-pure autonomic failure
-REM
-sleep behaviour disorder
Synucleinopathies cause
-metabolic impairment of alpha-synuclein
-leads to production of abnormal intracellular deposits or aggregation of insoluble fibrillary alpha-syn within neurons and glia
Parkinsons brain location
-caused by accumulation of alpha-synuclein in substania nigra which leads to degeneration of dopaminergic neurons
Dopaminergic neurons
-Primary source of dopamine in CNS
-Their loss is associated with PD
Alpha-synuclein
-predominantely expressed in brain
-Makes 1% of brain weight
-mainly found inside surface of membrane surrounding cell body and in presynaptic terminals
-correctly constructed pre-synaptic terminals are NB for nerve signals
Alpha-syn brain location
-mostly found in hippocampus, substania nigra and cerebellum and other place
Genetic proof of PD
At least 15% of people with PD have family history of it
Genetic variants in PD
LRRK2
PARK7
PINK1
PRKN
SNCA
these genes play a role in PD
LRRK2 gene role
-encodes dardarin protein
-gene is active in brain and other tissues
-protein has a leucine rich region
-leucine rich region plays a role in interacting with other proteins such as transmitting signals or assembling cell’s cytoskeleton
PRKN gene
-One of largest genes
-encodes for parkin protein
-Parkin tags damaged and excess proteins with ubiquitin to break them down
-Ubiquiton serves as signal to move unneeded proteins into proteasomes where they are degraded
Importance of ubiquition system
-ubiquitin-proteosome system is cells quality control system by disposing of damaged and excess proteins
-It regulates availibility of proteins involved in critical cell activities such as timing of cell division and growth
Parkin functions
-Ubiquiton-proteosome system
-Regulate suupply and release of synaptic vessicles from nerve cells
-It is an E3 ubiquitin ligase
causes of parkinsons
Misfolding of alpha synuclein
genetic factors
Parkinson’s spread throughout brain
Mechanism of spreading through interconnected neural networks
-Researchers suggest that the diseased cell releases alpha-synuclein which is taken up by normal adjacent cells
