Niemeyer Christine, Matosin Natalie, Kaul Dominic, Philipsen Alexandra, Gassen Nils C
Neurohomeostasis Research Group, Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany.
Faculty of Science, Medicine and Health, Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia.
Front Psychiatry. 2020 Jul 24;11:718. doi: 10.3389/fpsyt.2020.00718. eCollection 2020.
Cathepsins are proteases with functions in cellular homeostasis, lysosomal degradation and autophagy. Their role in the development of neurodegenerative diseases has been extensively studied. It is well established that impairment of proper cathepsin function plays a crucial role in the pathophysiology of neurodegenerative diseases, and in recent years a role for cathepsins in mental disorders has emerged given the involvement of cathepsins in memory function, hyperactivity, and in depression- and anxiety-like behavior. Here we review putative cathepsin functions with a special focus on their role in the pathophysiology of psychiatric diseases. Specifically, cathepsins are crucial for maintaining cellular homeostasis, particularly as part of the autophagy machinery of neural strategies underlying acute stress response. Disruption of cathepsin functions can lead to psychiatric diseases such as major depressive disease (MDD), bipolar disorder, and schizophrenia. Specifically, cathepsins can be excreted a process called secretory autophagy. Thereby, they are able to regulate extracellular factors such as brain-derived neurotrophic factor and perlecan c-terminal fragment LG3 providing maintenance of neuronal homeostasis and mediating neuronal plasticity in response to acute stress or trauma. In addition, impairment of proper cathepsin function can result in impaired synaptic transmission by compromised recycling and biogenesis of synaptic vesicles. Taken together, further investigations on cathepsin functions and stress response, neuroplasticity, and synaptic transmission will be of great interest in understanding the pathophysiology of psychiatric disorders.
组织蛋白酶是一类蛋白酶，在细胞内稳态、溶酶体降解和自噬过程中发挥作用。它们在神经退行性疾病发展过程中的作用已得到广泛研究。众所周知，组织蛋白酶功能异常在神经退行性疾病的病理生理学中起着关键作用，并且近年来，鉴于组织蛋白酶参与记忆功能、多动以及抑郁和焦虑样行为，其在精神障碍中的作用也逐渐显现。在此，我们综述组织蛋白酶的假定功能，特别关注它们在精神疾病病理生理学中的作用。具体而言，组织蛋白酶对于维持细胞内稳态至关重要，尤其是作为神经应对急性应激反应策略中自噬机制的一部分。组织蛋白酶功能的破坏可导致诸如重度抑郁症（MDD）、双相情感障碍和精神分裂症等精神疾病。具体来说，组织蛋白酶可以通过一种称为分泌性自噬的过程排出。由此，它们能够调节细胞外因子，如脑源性神经营养因子和基底膜聚糖C末端片段LG3，从而维持神经元内稳态并介导神经元可塑性以应对急性应激或创伤。此外，组织蛋白酶功能异常可导致突触小泡的再循环和生物合成受损，进而损害突触传递。综上所述，进一步研究组织蛋白酶的功能以及应激反应、神经可塑性和突触传递，对于理解精神障碍的病理生理学具有重要意义。
