Is Axonal Degeneration a Key Early Event in Parkinson’s Disease?

Article type: Research Article

Authors: Kurowska, Zuzanna^{a; b; *} | Kordower, Jeffrey H.^{c; d} | Stoessl, A. Jon^e | Burke, Robert E.^f | Brundin, Patrik^d | Yue, Zhenyu^g | Brady, Scott T.^h | Milbrandt, Jeffreyⁱ | Trapp, Bruce D.^{a; b} | Sherer, Todd B.^j | Medicetty, Satish^b

Affiliations: [a] Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA | [b] Renovo Neural Inc., Cleveland, OH, USA | [c] Research Center for Brain Repair, Rush University Medical Center, Chicago, IL, USA | [d] Van Andel Research Institute, Center for Neurodegenerative Science, Grand Rapids, MI, USA | [e] Pacific Parkinson’s Research Centre, Division of Neurology and Djavad Mowafaghian Centre for Brain Health, University of British Columbia and Vancouver Coastal Health, BC, Canada | [f] Departments of Neurology and Pathology & Cell Biology, Columbia University Medical Center, New York City, NY, USA | [g] Departments of Neurology and Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA | [h] Department of Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, IL, USA; Marine Biological Laboratory, Woods Hole, MA, USA | [i] Department of Genetics, Washington University School of Medicine in St. Louis, St. Louis, MO, USA; Hope Center for Neurological Disorders, Washington University School of Medicine in St. Louis, St. Louis, MO, USA | [j] The Michael J. Fox Foundation for Parkinson’s Research, New York, NY, USA

Correspondence: [*] Correspondence to: Dr. Zuzanna Kurowska, Department of Neurosciences, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA. Tel.: +1 21676 445 1860; Fax: +1 216 445 2981; E-mail: zkurowska@renovoneural.com.

Abstract: Recent research suggests that in Parkinson’s disease the long, thin and unmyelinated axons of dopaminergic neurons degenerate early in the disease process. We organized a workshop entitled ‘Axonal Pathology in Parkinson’s disease’, on March 23rd, 2016, in Cleveland, Ohio with the goals of summarizing the state-of-the-art and defining key gaps in knowledge. A group of eight research leaders discussed new developments in clinical pathology, functional imaging, animal models, and mechanisms of degeneration including neuroinflammation, autophagy and axonal transport deficits. While the workshop focused on PD, comparisons were made to other neurological conditions where axonal degeneration is well recognized.

Keywords: Parkinson disease, axons, animal disease models, autophagy, review, dopaminergic neurons, substantia nigra pars compacta, synapses, axonal transport, retrograde degeneration

DOI: 10.3233/JPD-160881

Journal: Journal of Parkinson's Disease, vol. 6, no. 4, pp. 703-707, 2016