Desplats P, Lee HJ, Bae EJ, et al. Inclusion formation and neuronal cell death through neuron-to-neuron transmission of alpha-synuclein. Proc Natl Acad Sci USA. 2009;106:13010-13015. [PubMed]

Recent studies have revealed Lewy body pathology in neurons grafted into the brains of patients with Parkinson’s disease (PD). In light of the fact that neural accumulation of α-synuclein and Lewy body formation are characteristic of PD and contribute to its progression, the mechanism underlying the pathology in grafted neurons is of vital interest. Now, research using a transgenic model of PD-like pathology has demonstrated transmission of α-synuclein from affected neurons in hosts to engrafted neuronal precursor cells.

α-Synuclein appeared to be transmitted via endocytosis to nearby neurons and neuronal precursor cells, resulting in the formation of Lewy-like inclusions. The accumulation of transmitted α-synuclein and the formation of Lewy-like inclusions were apparently promoted by the failure of protein “quality control” systems, particularly lysosomes. Additional in vitro and in vivo experiments demonstrated that cells exposed to neuron-derived α-synuclein exhibited signs of apoptosis, including nuclear fragmentation and activation of caspase 3.

The authors noted that the observed cell-to-cell transmission of α-synuclein provides important insights into mechanisms of progression in PD pathology and warrants further investigation.

Olanow CW, Rascol O, Hauser R, et al. A double-blind, delayed-start trial of rasagiline in Parkinson’s disease. N Engl J Med. 2009;361:1268-1278. [PubMed]

The search for a treatment capable of slowing clinical progression in Parkinson’s disease (PD) has generated intense interest. A recent effort focused on the identification of a potential disease-modifying effect (in addition to the established symptomatic effect) of rasagiline in doses of 1 or 2 mg/d. In a double-blind, delayed-start trial, 1,176 patients with early, untreated PD were randomized to receive either the 1-mg/d or the 2-mg/d dose of rasagiline for 72 weeks (defined as the early-start group) or to receive placebo for 36 weeks, then be switched to either the 1-mg/d or the 2-mg/d dose of rasagiline for the remaining 36 weeks (the delayed-start group).