A Possible Mechanism for the Propagation of Pathological Proteins in Parkinson’s Disease

Abstract

Parkinson’s disease is a common neurodegenerative disorder which recently has come to be regarded as a prion-like foldopathy, the latter term implying that the intercellular trafficking of abnormally folded proteins transmits disease between cells and produces pathology in target cells through the induction of a mis-folded state in normal protein in those cells. In the case of Parkinson’s disease, the prion-like protein primarily involved is alpha-synuclein and inclusions of this protein called Lewy Bodies are commonly found in the substantia nigra of affected patients. Over recent years considerable evidence has been developed to show that a variety of extracellular signaling molecules called intracrines can act in the intracellular space of their cells of synthesis or in target cells after intercellular trafficking. Thus there is some commonality between intracrinephysiology and the pathophysiology of prion-like foldopathies such as Parkinson’s disease. Here these issues and a possible nexus between Parkinson’s disease and intracrine biology are discussed. Abbreviations