Non-autonomous cell death in Parkinson's disease

Abstract

Parkinson's disease (PD) is a relentlessly progressive neurodegenerative disorder, characterised by symptoms of bradykinesia, rest tremor, and rigidity, due to the loss of dopamine (DA) neurons. Intracellular accumulation and aggregation of α-synuclein in Lewy bodies and neurites accompanies the loss of DA neurons. Why DA neurons degenerate and α-synuclein aggregates in patients with PD is poorly understood. Three recent articles in Nature Medicine provide important clues to the underlying degenerative process and suggest that the loss of DA neurons and the aggregation of α-synuclein is mediated, in part, by a non-cell-autonomous process. 1 Kordower JH Chu Y Hauser RA Freeman TB Olanow CW Lewy body-like pathology in long-term embryonic nigral transplants in Parkinson's disease. Nat Med. 2008; (published online Apr 6.)https://doi.org/10.1038/nm1747 Crossref PubMed Scopus (1200) Google Scholar , 2 Li JY Englund E Holton JL et al. Lewy bodies in grafted neurons in subjects with Parkinson's disease suggest host-to-graft disease propagation. Nat Med. 2008; (published online Apr 6.)https://doi.org/10.1038/nm1746 Crossref Scopus (1294) Google Scholar , 3 Mendez I Vinuela A Astradsson A et al. Dopamine neurons implanted into people with Parkinson's disease survive without pathology for 14 years. Nat Med. 2008; (published online Apr 6.)https://doi.org/10.1038/nm1752 Crossref PubMed Scopus (347) Google Scholar