Prymaczok Natalia C, Riek Roland, Gerez Juan
Laboratorio de Neurofisiología del Instituto Multidisciplinario de Biología Celular, Argentine Research Council (CONICET), National University of La Plata and Scientific Research Commission, Province of Buenos Aires (CIC-PBA) La Plata, Buenos Aires, Argentina.
Laboratory of Physical Chemistry, D-CHAB, ETH Zurich Zurich, Switzerland.
Front Hum Neurosci. 2016 Dec 2;10:608. doi: 10.3389/fnhum.2016.00608. eCollection 2016.
As Parkinson's disease progresses, a massive loss of dopaminergic neurons is accompanied by accumulation of alpha-Synuclein (αSyn) 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 αSyn, that can occur via sequential steps of secretion and uptake. Certain pathological forms of transmitted αSyn 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 αSyn focusing on its role in the progression of Parkinson's disease.
随着帕金森病的进展，多巴胺能神经元大量丧失，同时伴有α-突触核蛋白（αSyn）神经元内含物的积累，这些内含物被称为路易小体和路易神经突。内含物首先出现在嗅球和肠神经元中，然后出现在上升的神经解剖学相互连接区域，最后，在疾病晚期，在黑质致密部观察到路易小体，并伴有明显的神经元丧失迹象。据信，路易小体在神经系统中的传播是αSyn细胞间传播的结果，这可能通过分泌和摄取的连续步骤发生。某些病理性形式的传播性αSyn能够在健康受体细胞中播种内源性对应物，从而促进内含物形成、扩增和传播的自我维持循环，这最终是疾病进展的基础。在这里，我们回顾αSyn的细胞间传播，重点关注其在帕金森病进展中的作用。
