Week 1 Flashcards
characteristics of neurological diseases
1) Progressive neurological symptoms
2) Selective loss of neurons (SNc and basal ganglia)
3) Presence of protein aggregates
4) No curative treatments
Parkinson’s Disease
- Symptoms
- why is multifactorial
- what protein causes it
- motor deficits including
tremors, muscle rigidity, bradykinesia, and impaired gait - multifactorial disorder that has a strong environmental component, as less than 10% of cases are hereditary
- Aggregation of α-synuclein (αSyn) is thought to be pathogenic in
a family of diseases termed synucleinopathies, which includes PD,
multiple system atrophy, and Lewy body disease
what is the gene for a-synuclein?
Other genes indetified that contribute to PD (6)
- SNCA
- Lewy bodies, L-dopa, PRKN, PINK1, DJ-1, LRRK2
known causes of PD (Etiology) 3 things
- Cerebral atherosclerosis
- Viral encephalitis (inflammation of brain)
- Side effects of several antipsychotic drugs (i.e., phenothiazides, butyrophenones, reserpine
induce PD in mice
Toxicology models selectively destroy x and what are these models (6)
x= catecholaminergic neurons (contain dopaminergic system)
some toxicology models:
- Reserpine
- MPTP
- Methamphetamine
- 6-OH-dopamine
- Rotenone
- paraquat
-what was the H1N1 outbreak and how does it relate to PD
- 1918 H1N1 (flu outbreak), animals infected saw PD like symptoms,
PNAS Article
a mouse strain was infected with H5N1 without adaptation. What does that mean? How does this virus travel
- virus doesnt need to genetic ally change to infect humans from animals
- regardless of exposure site, virus will affect the brain. travels from peipheral nervous system to CNS
PNAS Article
- what was activated in regions infected by H5N1 virus and what was its duration
- what happens 60 days after infection
- what did these result suggests
- In regions infected by H5N1 virus, observed activation of microglia and alpha-synuclein phosphorylation and
aggregation that persists long after resolution of the infection. - A significant loss of dopaminergic neurons in the substantia nigra
pars compacta 60 days after infection - Results suggest that a pandemic H5N1 pathogen, or other neurotropic influenza virus, could initiate CNS disorders of protein aggregation including Parkinson’s and Alzheimer’s diseases.
What is TH? What does it do
Tyrosine Hydroxylase
enzyme that makes enzyme. the presence of TH means that we are looking at a dopaminergic neuron
what is a nucleoprotein
a marker for a virus
nucleoprotein + TH
infected dopaminergic neuron
Iba-1
pSer129SYN
DAP1
DAP1: Nuclear strain
pSer129SYN:
Ilba-1: marker for activated microgila
PNAS article
- in the CNS where was the H5N1 virus detected and where was it not
- the presence of virus in brainstem neurons was confirmed by what and where
- The A/Vietnam/1203/04 virus may enter the CNS via cranial nerves via what
- n the CNS, the H5N1 virus was detected in neurons and microglia but was not observed in astrocytes .
- The presence of virus in brainstem neurons was confirmed by transmission
electron microscopy, which revealed structures of the shape and size
characteristic of H5N1 influenza virus in the cytoplasm, axoplasm, and
nucleus - The A/Vietnam/1203/04 virus may enter the CNS via cranial nerves (via the
peripheral or enteric nerves),
Borna Disease Virus
- what is affected
- consequences in humans
- what is part of the replication machinery of BDV and its mRNA has been isolated from what
- This is a neurotropic virus that can infect various species (all mammals)
- In humans, some suggestion that perhaps many mood disorders
and psychoses including schizophrenia and depression are caused by this virus or remnants of this virus - Phosphoprotein 24 (P24) is part of the replication machinery of BDV and its mRNA has been isolated from the blood of patients with mood disorders
History of BDV and how it affects different people
Horses carried BDV and gave it to humans but the virus is expressed in different parts of the genome for different people and symptoms arise based on that
