Cal'MAM'ity at the Endoplasmic Reticulum-Mitochondrial Interface: A Potential Therapeutic Target for Neurodegeneration and Human Immunodeficiency Virus-Associated Neurocognitive Disorders.
Cal'MAM'ity at the Endoplasmic Reticulum-Mitochondrial Interface: A Potential Therapeutic Target for Neurodegeneration and Human Immunodeficiency Virus-Associated Neurocognitive Disorders.
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内质网-线粒体界面的Cal'MAM'ity：神经变性和人类免疫缺陷病毒相关神经认知障碍的潜在治疗靶点。
DOI：
10.3389/fnins.2021.715945
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发表时间：
2021
影响因子：
4.3
通讯作者：
Borgmann K
中科院分区：
文献类型：
--
作者：
Proulx J;Park IW;Borgmann K
内质网（ER）是一个多功能的细胞器，是细胞内钙储存、脂质生物合成、蛋白质合成和质量控制的主要场所。线粒体负责产生细胞存活和功能所需的大部分细胞能量，并且是许多代谢和信号传导过程的组成部分。线粒体相关的ER膜（MAM）是ER和线粒体之间的直接接触位点，其充当协调基本细胞过程的平台，所述基本细胞过程诸如线粒体动力学和生物能量学、钙和脂质稳态、自噬、凋亡、炎症和细胞内应激反应。鉴于MAM介导的机制在调节细胞命运和功能中的重要性，MAM现在被称为疾病病理学基础的关键分子和细胞枢纽。值得注意的是，神经元是唯一容易受到线粒体功能障碍和细胞内应激，这突出了MAMs作为操纵MAM相关机制的潜在靶点的重要性。然而，MAM通讯和连接的改变是否是疾病发展和进展中的致病因素或补偿机制仍然难以捉摸。无论如何，探索是必要的，以确定是否MAMs是治疗靶向打击神经退行性变。在这里，我们审查关键MAM相互作用和蛋白质在体外和体内模型阿尔茨海默氏病，帕金森氏病，肌萎缩侧索硬化症。我们进一步讨论MAMs在HIV相关神经认知障碍（HAND）中的意义，因为MAMs尚未在这种神经病理学中进行探索。这些观点特别关注线粒体功能障碍，钙调节异常和ER应激作为显着MAM介导的机制HAND病理学。最后，我们讨论了操纵MAM功能作为神经退行性疾病的治疗干预的潜在目标。未来的研究是必要的，以更好地了解MAMs在神经胶质功能障碍和神经毒性中的相互作用和治疗应用。
The endoplasmic reticulum (ER) is a multifunctional organelle and serves as the primary site for intracellular calcium storage, lipid biogenesis, protein synthesis, and quality control. Mitochondria are responsible for producing the majority of cellular energy required for cell survival and function and are integral for many metabolic and signaling processes. Mitochondria-associated ER membranes (MAMs) are direct contact sites between the ER and mitochondria that serve as platforms to coordinate fundamental cellular processes such as mitochondrial dynamics and bioenergetics, calcium and lipid homeostasis, autophagy, apoptosis, inflammation, and intracellular stress responses. Given the importance of MAM-mediated mechanisms in regulating cellular fate and function, MAMs are now known as key molecular and cellular hubs underlying disease pathology. Notably, neurons are uniquely susceptible to mitochondrial dysfunction and intracellular stress, which highlights the importance of MAMs as potential targets to manipulate MAM-associated mechanisms. However, whether altered MAM communication and connectivity are causative agents or compensatory mechanisms in disease development and progression remains elusive. Regardless, exploration is warranted to determine if MAMs are therapeutically targetable to combat neurodegeneration. Here, we review key MAM interactions and proteins both in vitro and in vivo models of Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis. We further discuss implications of MAMs in HIV-associated neurocognitive disorders (HAND), as MAMs have not yet been explored in this neuropathology. These perspectives specifically focus on mitochondrial dysfunction, calcium dysregulation and ER stress as notable MAM-mediated mechanisms underlying HAND pathology. Finally, we discuss potential targets to manipulate MAM function as a therapeutic intervention against neurodegeneration. Future investigations are warranted to better understand the interplay and therapeutic application of MAMs in glial dysfunction and neurotoxicity.
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影响因子：
4.6
作者：
Bravo-Sagua R;López-Crisosto C;Parra V;Rodriguez-Peña M;Rothermel BA;Quest AF;Lavandero S
通讯作者：
Lavandero S
影响因子：
32.4
作者：
Bronner DN;Abuaita BH;Chen X;Fitzgerald KA;Nuñez G;He Y;Yin XM;O'Riordan MX
通讯作者：
O'Riordan MX
影响因子：
1
作者：
Cisneros IE;Ghorpade A
通讯作者：
Ghorpade A
影响因子：
9
作者：
Bernard-Marissal N;Chrast R;Schneider BL
通讯作者：
Schneider BL
影响因子：
11.4
作者：
Area-Gomez, Estela;Castillo, Maria Del Carmen Lara;Tambini, Marc D.;Guardia-Laguarta, Cristina;de Groof, Ad J. C.;Madra, Moneek;Ikenouchi, Junichi;Umeda, Masato;Bird, Thomas D.;Sturley, Stephen L.;Schon, Eric A.
通讯作者：
Schon, Eric A.