The synaptic pathology of alpha-synuclein aggregation in dementia with Lewy bodies, Parkinson's disease and Parkinson's disease dementia.
The synaptic pathology of alpha-synuclein aggregation in dementia with Lewy bodies, Parkinson's disease and Parkinson's disease dementia.
复制标题
DOI：
10.1007/s00401-010-0711-0
复制
发表时间：
2010-08
影响因子：
12.7
通讯作者：
Schulz-Schaeffer WJ
中科院分区：
文献类型：
--
作者：
Schulz-Schaeffer WJ
帕金森病（PD）和路易体痴呆（DLB）通常与多巴胺能神经元的损失有关。黑质神经元的损失和在一些剩余的神经元中存在路易体内含物是在疾病的最后阶段观察到的标志性病理学。然而，试图将路易体病理学与细胞死亡或临床症状的严重程度相关联的尝试并不成功。虽然路易体很难解释神经退行性过程的病理生理学，但临床症状确实表明位于突触前的退行性过程导致神经递质缺乏。最近的研究表明，在DLB病例中，90%甚至更多的α-突触核蛋白聚集体以非常小的沉积物的形式位于突触前。与此同时，树突棘缩回，而突触前相对保留，表明神经递质剥夺。对于PD，可以证明相同的α-突触核蛋白病理学。这些发现提出了这样的观点，即不是细胞死亡而是α-突触核蛋白聚集体相关的突触功能障碍导致神经变性。这为理解PD和DLB打开了新的视角。如果突触前α-突触核蛋白聚集，而不是神经元丢失，是神经退行性过程的关键问题，那么PD和DLB最终可能在未来得到治疗。这种疾病可能通过跨突触传播而进展，这表明干细胞移植的用途有限。未来的治疗可能会集中在突触的再生上。
Parkinson’s disease (PD) and dementia with Lewy bodies (DLB) are usually associated with loss of dopaminergic neurons. Loss of substantia nigra neurons and presence of Lewy body inclusions in some of the remaining neurons are the hallmark pathology seen in the final stages of the disease. Attempts to correlate Lewy body pathology to either cell death or severity of clinical symptoms, however, have not been successful. While the pathophysiology of the neurodegenerative process can hardly be explained by Lewy bodies, the clinical symptoms do indicate a degenerative process located at the presynapse resulting in a neurotransmitter deficiency. Recently it was shown that 90% or even more of α-synuclein aggregates in DLB cases were located at the presynapses in the form of very small deposits. In parallel, dendritic spines are retracted, whereas the presynapses are relatively preserved, suggesting a neurotransmitter deprivation. The same α-synuclein pathology can be demonstrated for PD. These findings give rise to the notion that not cell death but rather α-synuclein aggregate-related synaptic dysfunction causes the neurodegeneration. This opens new perspectives for understanding PD and DLB. If presynaptic α-synuclein aggregation, not neuronal loss, is the key issue of the neurodegenerative process, then PD and DLB may eventually be treatable in the future. The disease may progress via trans-synaptical spread, suggesting that stem cell transplants are of limited use. Future therapies may focus on the regeneration of synapses.
登录
查看更多内容
影响因子：
82.9
作者：
Andréoletti, O;Simon, S;Schelcher, F
通讯作者：
Schelcher, F
DOI：
10.1046/j.1365-2990.2000.026002143.x
发表时间：
2000-04-01
影响因子：
5
作者：
Belichenko, PV;Brown, D;Fraser, JR
通讯作者：
Fraser, JR
影响因子：
2.9
作者：
Conway, KA;Harper, JD;Lansbury, PT
通讯作者：
Lansbury, PT
影响因子：
4.8
作者：
Bucciantini, M;Calloni, G;Stefani, M
通讯作者：
Stefani, M
影响因子：
5.3
作者：
Baglioni, Serena;Casamenti, Fiorella;Stefani, Massimo
通讯作者：
Stefani, Massimo