Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012 Jan;45(1):76-82.
doi: 10.1016/j.nbd.2010.10.022. Epub 2010 Nov 5.

Current status and future directions of gene expression profiling in Parkinson's disease

James G Greene  1
Affiliations
Review

Current status and future directions of gene expression profiling in Parkinson's disease

James G Greene. Neurobiol Dis. 2012 Jan.

Abstract

Parkinson's disease (PD) is a common age-associated neurodegenerative disorder. Motor symptoms are the cardinal component of PD, but non-motor symptoms, such as dementia, depression, and autonomic dysfunction are being increasingly recognized. Motor symptoms are primarily caused by selective degeneration of substantia nigra dopamine (SNDA) neurons in the midbrain; non-motor symptoms may be referable to well-described pathology at multiple levels of the neuraxis. Development of symptomatic and disease-modifying therapies is dependent on an accurate and comprehensive understanding of the pathogenesis and pathophysiology of PD. Gene expression profiling has been recently employed to assess function on a broad level in the hopes of gaining greater knowledge concerning how individual mechanisms of disease fit together as a whole and to generate novel hypotheses concerning PD pathogenesis, diagnosis, and progression. So far, the majority of studies have been performed on postmortem brain samples from PD patients, but more recently, studies have targeted enriched populations of dopamine neurons and have begun to explore extra-nigral neurons and even peripheral tissues. This review will provide a brief synopsis of gene expression profiling in parkinsonism and its pitfalls to date and propose several potential future directions and uses for the technique. It will focus on the use of microarray experiments to stimulate hypotheses concerning mechanisms of neurodegeneration in PD, since the majority of studies thus far have addressed that complicated issue.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Impact of sample composition and timing on gene expression profile
A. Photomicrograph of mouse midbrain stained for tyrosine hydroxylase (TH). Samples evaluated in parkinsonism (humans and mammalian models) have included whole midbrain, whole substantia nigra, SNC (substantia nigra pars compacta), including differentiation between medial (med) and lateral (lat). Dashed circles represent a sample of SNDA neurons obtainable by LCM. VTA, ventral tegmental area; SNR, substantia nigra pars reticulata. B. The graph depicts gene expression changes in the rotenone model of parkinsonism in rats with the ordinate axis being the composite expression change (vs. vehicle-treated) of five energy metabolism transcripts (ND1, NADH dehydrogenase subunit ND1; COX1, cytochrome c oxidase subunit 1; LDHB, lactate dehydrogenase B; TPI, triose phosphate isomerase 1; PDHC, pyruvate dehydrogenase subunit 1). There are four groups of animals: vehicle, very early (1 week of rotenone treatment), early (four weeks of treatment with no symptoms), and mid (symptomatic, with or without mild neurodegeneration). Note that sample composition impacts results, with dramatic differences between microdissected midbrain and laser-captured SNDA and VTADA neurons. Note also the substantial effect of time (disease stage) on the results from DA neurons.
Figure 2
Figure 2. Possible alterations in gene expression in parkinsonism
Theoretical schematic of PD progression depicts progressive damage from striatal dopamine terminals to SNDA cell bodies, including Lewy body formation, cell loss, and activation of microglia and astrocytes. Nigral gene expression patterns are below based on mammalian models and PD cases. Remember the caveat that correlation between gene expression experiments in PD is poor so far.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Adler CH. Nonmotor complications in Parkinson’s disease. Mov Disord. 2005;20(Suppl 11):S23–9. - PubMed
    1. Barone P, et al. The PRIAMO study: A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson’s disease. Mov Disord. 2009;24:1641–9. - PubMed
    1. Bassilana F, et al. Unraveling substantia nigra sequential gene expression in a progressive MPTP-lesioned macaque model of Parkinson’s disease. Neurobiol Dis. 2005;20:93–103. - PubMed
    1. Beach TG, et al. Multi-organ distribution of phosphorylated alpha-synuclein histopathology in subjects with Lewy body disorders. Acta Neuropathol. 2010;119:689–702. - PMC - PubMed
    1. Bossers K, et al. Analysis of gene expression in Parkinson’s disease: possible involvement of neurotrophic support and axon guidance in dopaminergic cell death. Brain Pathol. 2009;19:91–107. - PMC - PubMed

Publication types