Chapter 20 - Neurodegeneration Flashcards
Clinical features of Parkinson’s
resting tremor, difficulty in initiating movement (akinesia), slowing of movement in general (bradykinesia), less movement of facial muscles, rigidity in the joints, mostly motor related
Areas of the brain affected in Parkinson’s
Substantia nigra, basal ganglia
Cellular pathology of parkinson’s
loss of dopaminergic neurons in substantia nigra
known/potential causes of parkinson’s
no definitive cause
current treatments for parkinson’s
Levodopa (L-DOPA), a metabolite of tyrosine, the immediate precursor of DA (can cross BBB and convert to DA)
Other treatments aimed at increasing DA signaling in the brain
Pharmacological treatments for PD are primarily symptomatic,
not disease altering
Clinical features of Alzheimer’s
Begins insidiously, progresses gradually from forgetfulness and cognitive impairment, to physical problems, loss of communication skills, anhedonia, depression and withdrawal, and psychotic delusions and hallucinations
Areas of the brain affected in Alzheimer’s
Amyloid plaques and neurofibrillary tangles result in cell degeneration, especially in the frontotemporal association cortex
cellular pathology of Alzheimer’s
accumulation of beta-amyloid protein (β-amyloid, or A-beta [Aβ]) between neurons
In early stages neurofibrillary tangles (NFTs) are found in the entorhinal cortex, with progression to the hippocampus and neocortex
known/potential causes of Alzheimer’s
Advancing age, family history, obesity, untreated hypertension, high cholesterol, stress, sedentary lifestyle, head trauma or hypoxic brain injury, depression, bipolar disorder, PTSD
Genetic component of Alzheimer’s
Genes for (amyloid precursor protein) APP, on chromosome 21
Presenilin-1 (PS-1), on chromosome 14
Presenilin-2 (PS-2), on chromosome 1
treatments for alzheimer’s
Cholinesterase inhibitors: improve cognition by increasing ACh in the synapse
NMDA glutamate receptor antagonist memantine (Namenda) prevents excitotoxic neuron damage
Antibodies against phosphorylated tau proteins
Chemotherapy drugs that reduced tangles in mice
Spin-labeled fluorene compounds reduce plaque formation in cultures
Antibiotic treatments; tied to relationship between the gut microbiome and neuroinflammation
Clinical features of Huntington’s
Motor and cognitive symptoms result from degenerative effects on the basal ganglia, involuntary movement jerky or writhing, e rigidity, dystonia, problems with speech and swallowing, gait
problems, higher order thinking, and perserveration
Known cause of Huntington’s
A trinucleotide repeat (a CAG sequence) results in a gain-of-function mutation in the Huntington gene (HTT)
Likelihood of developing HD depends on the number of CAG repeats in the gene; complete penetrance at 40 repeats
current treatments for huntington’s
none can alter the course, Tetrabenazine (Xenazine) decreases the excessive movements, DA antagonist drugs, anticonvulsants, anxiolytic drugs, and antidepressants
clinical features of Amyotrophic lateral sclerosis (ALS)
Degeneration of spinal motor neurons manifests as tripping, clumsiness, dropping things, abnormal muscle fatigue.
Or it may begin with difficulty in chewing and swallowing and facial weakness, slurred speech
cellular pathology of ALS
Motor neurons show disruption of the cytoskeleton and aggregates of neurofilaments with other proteins to form “spheroids”
genetic factors of ALS
about 10% of cases are familial
potential causes of ALS
exposure to chemicals such as insecticides and pesticides
treatment for ALS
Riluzole (Rilutek) – presynaptic inhibitor of glutamate release; thought to provide benefit by blocking glutamate-mediated excitotoxicity
Edaravone (Radicava) - prevents oxidative stress damage to neurons
Botulinum toxin minimizes sialorrhea (excessive salivation and drooling)
Dextromethorphan HBR and quinidine sulfate (Nuedexta) for PBA
Clinical features of Multiple sclerosis (MS)
Fatigue, numbness/tingling
Walking/balance/coordination problems
Bladder and/or bowel dysfunction; sexual dysfunction
Vision problems, dizziness and vertigo
Cognitive dysfunction, emotional changes
Spasticity
areas of the brain affected in MS
autoimmune disorder; result of chronic attack on the myelin produced by oligodendrocytes in the brain, spinal cord, and optic nerves
how to diagnose MS
One must have lesions in at least two distinct areas of the CNS or
optic nerves
Or combinations of lesions, symptoms, CSF oligoclonal bands, or
progression of disease
potential/known causes of MS
Risk is greater in people who live above 40° latitude in the Northern Hemisphere up to the age of 15
- Protective vitamin D may be a factor
Environmental toxins and infections such as measles may increase risk
There seems to be some genetic component
treatments for MS
Treatments may be disease modifying or intended to treat an acute exacerbation, or to treat specific symptoms
Other treatments include monoclonal antibodies and chemotherapy drugs, to suppress elements of the immune system