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Is elevated norepinephrine an etiological factor in some cases of Parkinson’s disease?

Authors
  • Fitzgerald, Paul J.1, 2
  • 1 Department of Psychology
  • 2 Texas A&M University
Type
Published Article
Journal
Medical Hypotheses
Publisher
Elsevier
Publication Date
Jan 01, 2014
Accepted Date
Jan 22, 2014
Volume
82
Issue
4
Pages
462–469
Identifiers
DOI: 10.1002/ana.23687
Source
Elsevier
License
Unknown

Abstract

It is well documented that norepinephrine (NE) releasing neurons in the locus coeruleus, a brainstem nucleus that is a major source of NE for the brain, degenerate during the progression of Parkinson’s disease (PD). A number of studies also suggest that, as a result, there is less NE released in the brain during disease progression, which may contribute to the pathophysiology and symptomatology of PD. This paper puts forth the novel hypothesis that NE degeneration in PD is preceded by elevated NE signaling, mainly as a result of genetics, and that this elevation is a major etiological factor in the disease. In this scenario, long-term (if not lifelong) elevated NE signaling could eventually invoke compensatory mechanisms that result in noradrenergic, and possibly dopaminergic, cell death. Several lines of evidence are briefly reviewed on the relationship between NE signaling and PD, including studies of: the level of NE; drugs that increase or decrease NE signaling; the relationship between PD and bipolar disorder, hypertension, and obesity, since the latter three conditions may be associated with increased NE signaling; and the relationship between PD and psychological stress, since stress is associated with increased release of NE. Many of these studies support NE degeneration during the disease, although some are consistent with elevated NE signaling during disease progression. Because there are few data on the state of the NE system prior to disease onset, the central point of this paper that NE signaling is elevated prior to development of PD, remains largely hypothetical. If elevated NE signaling really is an etiological factor in this disease, then early identification of susceptible individuals and long-term treatment with NE transmission reducing drugs, may help prevent or slow progression of PD.

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