Exam 3 D1 Parkinson's Disease

Question 1

Parkinson’s Disease

Answer 1

neurodegenerative disorder that affects predominantly dopamine-producing (“dopaminergic”) neurons in a specific area of the brain called substantial nigra, which is a part of the basal ganglia

Question 2

at what rate do symptoms generally develop?

Answer 2

slowly over years; progression of symptoms can be different from person to person because of the diversity of the disease

Question 3

what are symptoms of Parkinson’s?

Answer 3

tremor (mainly at rest and described as pill rolling tremor in hands), slowness of movements (bradykinesia), limb rigidity, gait and balance problems

Question 4

what are people with Parkinson’s often more affected by?

Answer 4

non-motor symptoms rather than motor symptoms

Question 5

non-motor Parkinson’s symptoms

Answer 5

apathy, depression, constipation, sleep behavior disorders, loss of sense of smell, and cognitive impairment

Question 6

what are possible links to Parkinson’s?

Answer 6

exposure to pesticides and a history of head injury, but the risks are modest

Question 7

why do people with Parkinson’s first start experiencing symptoms later in the course of the disease?

Answer 7

because a significant amount of the subtantia nigra neurons have already been lost or impaired

Question 8

what are found in the substantia nigra neurons of Parkinson’s Disease patients?

Answer 8

Lewy bodies (accumulation of abnormal alpha-synuclein)

Question 9

what are Lewy bodies?

Answer 9

abnormal aggregates of protein that develop inside the nerve cells in Parkinson’s disease, Lewy body dementia, and some other disorders

Question 10

how are Lewy bodies identified?

Answer 10

under the microscope when histology is performed on the brain

Question 11

how do Lewy bodies appear?

Answer 11

as spherical masses that displace other cell components

Question 12

where are Lewy bodies found?

Answer 12

in the brainstem (within the substantia nigra) or within the cortex

Question 13

what are Lewy bodies composed of?

Answer 13

the protein alpha-synuclein associated with other proteins, such as ubiquitin, neurofilament protein, and alpha B crystalline. Tau proteins may also be present, and Lewy bodies may occasionally be surrounded by neurofibrillary tangles

Question 14

what can Lewy bodies occasionally exist with in the same neuron, particularly in the amygdala?

Answer 14

neurofibrillary tangles (NFTs)

Question 15

Alpha-synuclein

Answer 15

protein that is abundant in the human brain; smaller amounts are found in the heart, muscles, and other tissues

Question 16

where is alpha-synuclein mainly found in the brain?

Answer 16

mainly in presynaptic terminals

Question 17

what occurs with alpha-synclein in the presynaptic terminals of brain neurons?

Answer 17

alpha-synuclein interacts with phospholipids and proteins

Question 18

what is the possible function of alpha-synuclein?

Answer 18

plays a role in maintaining a supply of synaptic vesicles in presynaptic terminals by clustering synaptic vesicles; it may also help regulate the release of dopamine (NT critical for controlling the start and stop of voluntary and involuntary movements)

Question 19

what percent of synuclein is membrane-bound at any moment in neurons?

Answer 19

15%

Question 20

when/where is alpha-synuclein upregulated?

Answer 20

specifically in a discrete population of presynaptic terminals of the brain during a period of acquisition-related synaptic rearrangement

Question 21

what occurs when alpha-synuclein is upregulated?

Answer 21

it significantly interacts with tubulin, and it may have activity as a potential microtubule-associated protein, like tau

Question 22

what is the apparent function of alpha-synuclein?

Answer 22

molecular chaperone in the formation of SNARE complexes; in particular, it simultaneously binds to the phospholipids of the plasma membrane via its N-terminus domain and to synaptobrevin-2 via its C-terminus domain with increased importance during synaptic activity

Question 23

there is growing evidence that alpha-synuclein is involved in what?

Answer 23

the functioning of neuronal Golgi apparatus and vesicle trafficking

Question 24

what is alpha-nuclein apparently essential for?

Answer 24

normal development of the cognitive functions; knock-out mice with the targeted inactivation of the expression of alpha-synuclein show impaired spatial learning and working memory