Exam 3 D1 Parkinson's Disease Flashcards
Parkinson’s Disease
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
at what rate do symptoms generally develop?
slowly over years; progression of symptoms can be different from person to person because of the diversity of the disease
what are symptoms of Parkinson’s?
tremor (mainly at rest and described as pill rolling tremor in hands), slowness of movements (bradykinesia), limb rigidity, gait and balance problems
what are people with Parkinson’s often more affected by?
non-motor symptoms rather than motor symptoms
non-motor Parkinson’s symptoms
apathy, depression, constipation, sleep behavior disorders, loss of sense of smell, and cognitive impairment
what are possible links to Parkinson’s?
exposure to pesticides and a history of head injury, but the risks are modest
why do people with Parkinson’s first start experiencing symptoms later in the course of the disease?
because a significant amount of the subtantia nigra neurons have already been lost or impaired
what are found in the substantia nigra neurons of Parkinson’s Disease patients?
Lewy bodies (accumulation of abnormal alpha-synuclein)
what are Lewy bodies?
abnormal aggregates of protein that develop inside the nerve cells in Parkinson’s disease, Lewy body dementia, and some other disorders
how are Lewy bodies identified?
under the microscope when histology is performed on the brain
how do Lewy bodies appear?
as spherical masses that displace other cell components
where are Lewy bodies found?
in the brainstem (within the substantia nigra) or within the cortex
what are Lewy bodies composed of?
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
what can Lewy bodies occasionally exist with in the same neuron, particularly in the amygdala?
neurofibrillary tangles (NFTs)
Alpha-synuclein
protein that is abundant in the human brain; smaller amounts are found in the heart, muscles, and other tissues
where is alpha-synuclein mainly found in the brain?
mainly in presynaptic terminals
what occurs with alpha-synclein in the presynaptic terminals of brain neurons?
alpha-synuclein interacts with phospholipids and proteins
what is the possible function of alpha-synuclein?
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)
what percent of synuclein is membrane-bound at any moment in neurons?
15%
when/where is alpha-synuclein upregulated?
specifically in a discrete population of presynaptic terminals of the brain during a period of acquisition-related synaptic rearrangement
what occurs when alpha-synuclein is upregulated?
it significantly interacts with tubulin, and it may have activity as a potential microtubule-associated protein, like tau
what is the apparent function of alpha-synuclein?
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
there is growing evidence that alpha-synuclein is involved in what?
the functioning of neuronal Golgi apparatus and vesicle trafficking
what is alpha-nuclein apparently essential for?
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
