More than a Rumor Spreads in Parkinson's Disease

As Parkinson's disease progresses, a massive loss of dopaminergic neurons is accompanied by accumulation of alpha-Synuclein (alpha Syn) neuronal inclusions called Lewy bodies and Lewy neurites. Inclusions first appear in olfactory bulb and enteric neurons then in ascendant neuroanatomical interconnected areas, and finally, in late stages of the disease, Lewy bodies are observed in a substantia nigra pars compacta with clear signs of neuronal loss. It is believed that the spreading of Lewy bodies through the nervous system is a consequence of the cell-to-cell propagation of alpha Syn, that can occur via sequential steps of secretion and uptake. Certain pathological forms of transmitted alpha Syn are able to seed endogenous counterparts in healthy recipient cells, thus promoting the self-sustained cycle of inclusion formation, amplification and spreading, that ultimately underlies disease progression. Here we review the cell-to-cell propagation of alpha Syn focusing on its role in the progression of Parkinson's disease.