Bar-Yosef Tamara, Damri Odeya, Agam Galila
Department of Clinical Biochemistry and Pharmacology and Psychiatry Research Unit, Faculty of Health Sciences, Ben-Gurion University of the Negev and Mental Health Center, Beersheba, Israel.
Front Cell Neurosci. 2019 May 28;13:196. doi: 10.3389/fncel.2019.00196. eCollection 2019.
Autophagy is a vital lysosomal degradation and recycling pathway in the eukaryotic cell, responsible for maintaining an intricate balance between cell survival and cell death, necessary for neuronal survival and function. This dual role played by autophagy raises the question whether this process is a protective or a destructive pathway, the contributor of neuronal cell death or a failed attempt to repair aberrant processes? Deregulated autophagy at different steps of the pathway, whether excessive or downregulated, has been proposed to be associated with neurodegenerative disorders such as Alzheimer's-, Huntington's-, and Parkinson's-disease, known for their intracellular accumulation of protein aggregates. Recent observations of impaired autophagy also appeared in psychiatric disorders such as schizophrenia and bipolar disorder suggesting an additional contribution to the pathophysiology of mental illness. Here we review the current understanding of autophagy's role in various neuropsychiatric disorders and, hitherto, the prevailing new potential autophagy-related therapeutic strategies for their treatment.
自噬是真核细胞中一种重要的溶酶体降解和循环途径,负责维持细胞存活与细胞死亡之间的复杂平衡,这对神经元的存活和功能至关重要。自噬所发挥的这种双重作用引发了一个问题:这个过程是一条保护性还是破坏性途径,是神经元细胞死亡的促成因素还是修复异常过程的失败尝试?有人提出,在该途径的不同步骤中自噬失调,无论是过度还是下调,都与神经退行性疾病如阿尔茨海默病、亨廷顿病和帕金森病有关,这些疾病以细胞内蛋白质聚集体积累为特征。最近在精神分裂症和双相情感障碍等精神疾病中也出现了自噬受损的观察结果,这表明自噬对精神疾病的病理生理学也有额外影响。在此,我们综述了目前对自噬在各种神经精神疾病中作用的理解,以及迄今为止针对这些疾病流行的新的潜在自噬相关治疗策略。