Weber Audrey J, Herskowitz Jeremy H
Center for Neurodegeneration and Experimental Therapeutics, Departments of Neurology and Neurobiology, University of Alabama at Birmingham, Birmingham, AL, United States.
Front Cell Neurosci. 2021 Mar 15;15:636017. doi: 10.3389/fncel.2021.636017. eCollection 2021.
Rho-associated coiled-coil containing kinase isoform 2 (ROCK2) is a member of the AGC family of serine/threonine kinases and an extensively studied regulator of actin-mediated cytoskeleton contractility. Over the past decade, new evidence has emerged that suggests ROCK2 regulates autophagy. Recent studies indicate that dysregulation of autophagy contributes to the development of misfolded tau aggregates among entorhinal cortex (EC) excitatory neurons in early Alzheimer's disease (AD). While the accumulation of tau oligomers and fibrils is toxic to neurons, autophagy facilitates the degradation of these pathologic species and represents a major cellular pathway for tau disposal in neurons. ROCK2 is expressed in excitatory neurons and pharmacologic inhibition of ROCK2 can induce autophagy pathways. In this mini-review, we explore potential mechanisms by which ROCK2 mediates autophagy and actin dynamics and discuss how these pathways represent therapeutic avenues for Alzheimer's disease.
Rho相关卷曲螺旋结构域蛋白激酶2（ROCK2）是丝氨酸/苏氨酸激酶AGC家族的成员，也是一种对肌动蛋白介导的细胞骨架收缩性进行了广泛研究的调节因子。在过去十年中，出现了新的证据表明ROCK2调节自噬。最近的研究表明，自噬失调促成了早期阿尔茨海默病（AD）内嗅皮质（EC）兴奋性神经元中错误折叠的tau聚集体的形成。虽然tau寡聚体和原纤维的积累对神经元有毒性，但自噬促进了这些病理性物质的降解，并且是神经元中tau清除的主要细胞途径。ROCK2在兴奋性神经元中表达，对ROCK2的药理学抑制可诱导自噬途径。在本综述中，我们探讨了ROCK2介导自噬和肌动蛋白动力学的潜在机制，并讨论了这些途径如何代表阿尔茨海默病的治疗途径。
