Parkinson’s Disease and Heroin. Raymond Gan Veeral Gohil Vincent Lam Victoria Leung . PHM142 Fall 2012 Coordinator: Dr. Jeffrey Henderson Instructor: Dr. David Hampson. Overview. Parkinson’s Disease Overview and Symptoms General Information for Parkinson’s Disease
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Vincent Lam Victoria Leung
PHM142 Fall 2012
Coordinator: Dr. Jeffrey Henderson
Instructor: Dr. David Hampson
What is Parkinson’s Disease?
part of brain that controls movement
Exact cause is unknown
Parkinson’s Disease causes dopamine-producing cells in the substantianigra to die
Used a lentivirus-mediated NOX1 shRNAoverexpression to knock down NOX1.
PQ-induced α-synuclein aggregation was lower in cells with overexpressed NOX1 shRNA. (2.5 fold decrease)
Summary: NOX1 responsible for mediation of PQ-mediated oxidative stress.
Misfolded α- synuclein and oxidative stress impacts PD. α- synuclein activates microglia which increases the antioxidant enzyme expression. Mediated though by Nrf2.
Microglia are the immune cells in the brain that respond to changes in the brain’s environment.
A) coiled structure α-synuclein= inactivated microglia.
B) Misfolding. Protofibrils stabilized by dopamine. Increased microglial expression of antioxidant enzymes. Proinflammatory response
C) α- synuclein fibrils directly activate proinflammatory pathway. These cells become toxic to neurons surrounding it. Oxidative stress -> activated microglia->increased dopamine neuron dysfunction.
What is Heroin?
Routes of Administration:
Routes of Administration:
How was the connection found?
- Initially, they thought there was no connection between the two, but in 1982, they found a heroin addict that exhibited Parkinsonian symptoms.
This was atypical because Parkinson’s Disease mostly affects older people.
Discovered that these symptoms were a result of the abuse of synthetic heroin
Cell death &
Cristovao, A.C. (2012) NADPH Oxidase 1 Mediates α-synucleinopathy in Parkinson’s Disease. The Journal of Neuroscience, 32 (42), 14465-14477. doi: 10.1523/jneurosci.2246-12.2012
Beraud, D. 2012. Microglial Activation and Antioxidant Responses Induced by the Parkinson’s Disease Protein α-synuclein. J NeuroimmunePharmacol. doi: 10.1007/s11481-012-9401-0
Rzepa, H. (2011). “Morphine and heroin”. http://www.ch.ic.ac.uk/rzepa/mim/drugs/html/morphine.htm
London, E. (2011). “Heroin in the brain- its chemistry and effects”. http://www.pbs.org/wgbh/pages/frontline/shows/heroin/brain/
National Institute of Drug Abuse. (2010). “Heroin”. http://www.drugabuse.gov/publications/drugfacts/heroin