16 - PD

Question 1

PD: primarily caused by loss of? men vs. women?

Answer 1

gradual loss of DA producing neurons in SN pars compacta and striatum. men get it at a higher rate, 2:1

Question 2

PD: prevalence? # people affected?

Answer 2

2nd most prevalent ND disease. over 1 million US, 130 000 Cads.

Question 3

7 major functions of DA

Answer 3

control/regulation of bevhaiour. mental health. voluntary movement. reward seeking behaviour. memory. ability to learn. secretion of prolactin from ant pit.

Question 4

3 DA pathways

Answer 4

nigrostriatal. mesolimbic/mesocortical. tuberinfundibular.

Question 5

most neurons that produce DA originate in? name of brain part?

Answer 5

ventral midbrain: substantia nigra and ventral tegmental area. midbrain = mesencephalon

Question 6

where to SN neurons project to? two parts of SN?

Answer 6

project to striatum to regulate motor control. pars compacta + pars reticulata.

Question 7

pars compacta vs. pars reticulata

Answer 7

compacta: input to basal ganglia circuit, main DA conduit to striatum. reticulata: major ouput from BG, mostly GABA neurons and go to extrinsic structures

Question 8

DA neurons: what enzymes? also expresses high lllevels of? expresses what transporter?

Answer 8

tyrosine hydroxylase and l-aromatic amino acid decarboxylase to make DA. neuromelanin. dopamine active transporter

Question 9

neuromenalin: does what?

Answer 9

makes DA neurons appear blackened. by product of dopamine metabolism by MAO. might be protective against oxidative stress; decreased neuromelanin = increased neurotoxicity

Question 10

development of DA neurons: what signal?

Answer 10

SHH sonic hedge hog; induces ventral cells

Question 11

2 major forms of DP?

Answer 11

familial = genetic aberrations + mutations. idiopathic = combo of genetic suscpebility + enviornment factors

Question 12

risk factors for PD

Answer 12

familiar genetic risk factors. exogenous neurotoxins. insecticides, herbicides, infections, cranial trauma, stress, age

Question 13

6 major genes for familial PD

Answer 13

SNCA for a synuclein. Prkn = parkin. LRRK 2. PINK1. UCHL 1. DJ 1

Question 14

DA neurotoxicity associated with what features?

Answer 14

lewy body formation. abnormalities in protein degradation. protein trafficking. mitochondrial malfunction. microtubule assembly. embryonic development. inflmammation

Question 15

autosomal dominant: what 3 proteins?

Answer 15

a-synuclein. LRRK2. UCHL1 –> gain of function

Question 16

autosomal recessive: what mutations?

Answer 16

Parkin, PINK1, DJ1 –> loss of function

Question 17

a synuclein: expressed where? localized? associated with?

Answer 17

highly expressed throughout NS, esp in presynp terminals. significant localized with vesicles associated with vesicular transport; can be found associated with membrane lipids

Question 18

LRRK2: aka? important for? also involved in?

Answer 18

Dardarin. important signalling molecule. also involved with other NDDs like AD>

Question 19

LRRK2: lcoalized? involved in what processes? mutations and PD?

Answer 19

cytoplasm, membraneous organelles, mitochondria, plasma membrane. endosomal recycling, signalling pathways. pts with LRRK2 mutations = milder, more treatable.

Question 20

UCHL 1: abundance? found where?

Answer 20

highly abundant total brain protein. found mostly in neurons and neuroendocrine cells.

Question 21

UCHL 1: what function?

Answer 21

involved in recyling of ubiquitin: de-ubiquinating enzyme, and so protects protein from degradation

Question 22

overexpress UCHL1 = what?

Answer 22

accumulation of a-synuclein