Flashcards in 16 - PD Deck (22):
PD: primarily caused by loss of? men vs. women?
gradual loss of DA producing neurons in SN pars compacta and striatum. men get it at a higher rate, 2:1
PD: prevalence? # people affected?
2nd most prevalent ND disease. over 1 million US, 130 000 Cads.
7 major functions of DA
control/regulation of bevhaiour. mental health. voluntary movement. reward seeking behaviour. memory. ability to learn. secretion of prolactin from ant pit.
3 DA pathways
nigrostriatal. mesolimbic/mesocortical. tuberinfundibular.
most neurons that produce DA originate in? name of brain part?
ventral midbrain: substantia nigra and ventral tegmental area. midbrain = mesencephalon
where to SN neurons project to? two parts of SN?
project to striatum to regulate motor control. pars compacta + pars reticulata.
pars compacta vs. pars reticulata
compacta: input to basal ganglia circuit, main DA conduit to striatum. reticulata: major ouput from BG, mostly GABA neurons and go to extrinsic structures
DA neurons: what enzymes? also expresses high lllevels of? expresses what transporter?
tyrosine hydroxylase and l-aromatic amino acid decarboxylase to make DA. neuromelanin. dopamine active transporter
neuromenalin: does what?
makes DA neurons appear blackened. by product of dopamine metabolism by MAO. might be protective against oxidative stress; decreased neuromelanin = increased neurotoxicity
development of DA neurons: what signal?
SHH sonic hedge hog; induces ventral cells
2 major forms of DP?
familial = genetic aberrations + mutations. idiopathic = combo of genetic suscpebility + enviornment factors
risk factors for PD
familiar genetic risk factors. exogenous neurotoxins. insecticides, herbicides, infections, cranial trauma, stress, age
6 major genes for familial PD
SNCA for a synuclein. Prkn = parkin. LRRK 2. PINK1. UCHL 1. DJ 1
DA neurotoxicity associated with what features?
lewy body formation. abnormalities in protein degradation. protein trafficking. mitochondrial malfunction. microtubule assembly. embryonic development. inflmammation
autosomal dominant: what 3 proteins?
a-synuclein. LRRK2. UCHL1 --> gain of function
autosomal recessive: what mutations?
Parkin, PINK1, DJ1 --> loss of function
a synuclein: expressed where? localized? associated with?
highly expressed throughout NS, esp in presynp terminals. significant localized with vesicles associated with vesicular transport; can be found associated with membrane lipids
LRRK2: aka? important for? also involved in?
Dardarin. important signalling molecule. also involved with other NDDs like AD>
LRRK2: lcoalized? involved in what processes? mutations and PD?
cytoplasm, membraneous organelles, mitochondria, plasma membrane. endosomal recycling, signalling pathways. pts with LRRK2 mutations = milder, more treatable.
UCHL 1: abundance? found where?
highly abundant total brain protein. found mostly in neurons and neuroendocrine cells.
UCHL 1: what function?
involved in recyling of ubiquitin: de-ubiquinating enzyme, and so protects protein from degradation