1: Cell Transplant. 2008;17(4):363-72.

Neuroinflammation and peripheral immune infiltration in Parkinson's disease: an
autoimmune hypothesis.

Monahan AJ, Warren M, Carvey PM.

Department of Pharmacology, Rush University Medical Center, Chicago, IL 60612,
USA. Angela_Monahan@rush.edu

Despite decades of research and the development of a large group of animal
models, our understanding of the mechanisms responsible for the progressive loss
of dopamine neurons in Parkinson's disease (PD) is unknown. So-called
neuroprotective studies demonstrate that a vast group of molecules readily
attenuate the dopamine (DA) neuron loss produced by DA neurotoxin insult. Despite
these successes, these neuroprotective strategies have been surprisingly
ineffective in patients. This may reflect the fact that the initial pathogenic
event and the subsequent disease progression is a consequence of different
mechanisms. As we began to think about this disconnect, we discovered that
animals exposed to DA neurotoxins exhibited blood-brain barrier (BBB)
dysfunction. If the BBB in PD patients is disrupted, then the barrier that
normally segregates peripheral vascular factors from brain parenchyma is no
longer present. Immune cells could then enter brain and produce a
self-perpetuating (progressive) degenerative process. In this review, we propose
that peripheral immunity contributes to the degenerative process of PD and may be
responsible for the progressive nature of the disease. This hypothesis is
supported by a broad and diverse literature that is just beginning to come
together to suggest that PD is, in part, an autoimmune disease. In order to
understand this hypothesis, the reader must question the conventional wisdom that
the BBB is intact in PD, the brain is an immune privileged area, and that
pathogenic insult and disease progression may reflect different mechanisms.


PMID: 18522239 [PubMed - indexed for MEDLINE]