Impact of alpha-synuclein pathology on adult neurogenesis: evidence for multilayered mechanisms

Jana Bonsberger; Franziska Richter; Milos Stanojlovic

摘要：Parkinson's disease (PD) is the second most common neurodegenerative disease affecting 8–10 million people worldwide. Moreover, PD is the fastest-growing neurodegenerative disease and it is predicted that the number of patients will double in the next thirty years. Neuropathologically, PD is characterized by the presence of protein aggregations called Lewy bodies (LB) and by degeneration of dopaminergic neurons in the substantia nigra pars compacta, which give rise to classical motor symptoms. However, overwhelming scientific evidence shows that PD is a multilayered disease. LB pathology affects different brain regions and neuronal populations leading to various non-motor symptoms, such as cognitive, sleep, and sensory impairments, mood and metabolic disorders, etc., some of which, interestingly, appear long before the hallmark motor symptoms. A main component of LB is the protein alpha-synuclein (α-syn). Accumulation and aggregation of α-syn is a characteristic feature that can be observed in synucleinopathies, a group of diseases which PD, dementia with Lewy bodies (DLB), and multiple system atrophy belongs to. While DLB is characterized by progressive dementia, about 80％ of PD patients experience some form of cognitive impairment. Therefore, PD and DLB together constitute the second leading cause of neurodegenerative dementias. Moreover, it is proposed that α-syn-associated pathology in cortical and hippocampal (Hipp) brain areas is causing cognitive deficits and dementia in PD and DLB. Alterations in adult neurogenesis may represent a potential pathomechanism.