ROCK2 inhibition: A futuristic approach for the management of Alzheimer's disease

被引：19

作者：

Mani, Shalini ^{[1
]}

Jindal, Divya ^{[1
]}

Chopra, Hitesh ^{[2
]}

Jha, Saurabh Kumar ^{[3
,4
,5
]}

Singh, Sachin Kumar ^{[6
]}

Ashraf, Gulam Md ^{[7
]}

Kamal, Mehnaz ^{[8
]}

Iqbal, Danish ^{[9
]}

Chellappan, Dinesh Kumar ^{[10
]}

Dey, Abhijit ^{[11
]}

Dewanjee, Saikat ^{[12
]}

Singh, Keshav K. ^{[13
]}

Ojha, Shreesh ^{[14
]}

Singh, Inderbir ^{[15
]}

Gautam, Rupesh K. ^{[15
]}

Jha, Niraj Kumar ^{[3
,4
,5
]}

机构：

[1] Jaypee Inst Informat Technol, Ctr Emerging Dis, Dept Biotechnol, Noida, UP, India

[2] Chitkara Univ, Chitkara Coll Pharm, Rajpura, Punjab, India

[3] Sharda Univ, Sch Engn & Technol SET, Dept Biotechnol, Knowledge Pk 3, Greater Noida 201310, Uttar Pradesh, India

[4] Uttaranchal Univ, Sch Appl & Life Sci SALS, Dept Biotechnol, Dehra Dun 248007, Uttarakhand, India

[5] Chandigarh Univ, Dept Biotechnol Engn & Food Technol, Mohali 140413, India

[6] Lovely Profess Univ, Sch Pharmaceut Sci, Phagwara 144411, Punjab, India

[7] King Fahd Med Res Ctr, Riyadh, Saudi Arabia

[8] Prince Sattam Bin Abdulaziz Univ, Coll Pharm, Dept Pharmaceut Chem, Al Kharj 11942, Saudi Arabia

[9] Majmaah Univ, Coll Appl Med Sci, Dept Med Lab Sci, Majmaah 11952, Saudi Arabia

[10] Int Med Univ, Dept Life Sci, Kuala Lumpur, Malaysia

[11] Presidency Univ, Dept Life Sci, 86-1 Coll St, Kolkata 700073, India

[12] Jadavpur Univ, Dept Pharmaceut Technol, Adv Pharmacognosy Res Lab, Kolkata 700032, India

[13] Univ Alabama Birmingham, Dept Genet, UAB Sch Med, Birmingham, AL USA

[14] United Arab Emirates Univ, Dept Pharmacol & Therapeut, Coll Med & Hlth Sci, POB 15551, Abu Dhabi, U Arab Emirates

[15] Indore Inst Pharm, Dept Pharmacol, Indore 453331, India

来源：

NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS | 2022年 / 142卷

关键词：

Neurodegeneration; Alzheimer?s disease; ROCK; Mitophagy; Parkin; Mitochondria; Neuroprotection; RHO-KINASE INHIBITOR; DYNAMIN-RELATED GTPASE; CENTRAL-NERVOUS-SYSTEM; AMYLOID-BETA; MITOCHONDRIAL DYNAMICS; COGNITIVE IMPAIRMENT; THERAPEUTIC TARGET; RHO/ROCK PATHWAY; IN-VITRO; INDUCED NEUROTOXICITY;

D O I：

10.1016/j.neubiorev.2022.104871

中图分类号：

B84 [心理学]; C [社会科学总论]; Q98 [人类学];

学科分类号：

03 ; 0303 ; 030303 ; 04 ; 0402 ;

摘要：

Neurons depend on mitochondrial functions for membrane excitability, neurotransmission, and plasticity. Mitochondrial dynamics are important for neural cell maintenance. To maintain mitochondrial homeostasis, lysosomes remove dysfunctional mitochondria through mitophagy. Mitophagy promotes mitochondrial turnover and prevents the accumulation of dysfunctional mitochondria. In many neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), mitophagy is disrupted in neurons. Mitophagy is regulated by several pro-teins; recently, Rho-associated coiled-coil containing protein kinase 2 (ROCK2) has been suggested to negatively regulate the Parkin-dependent mitophagy pathway. Thus, ROCK2 inhibition may be a promising therapy for NDDs. This review summarizes the mitophagy pathway, the role of ROCK2 in Parkin-dependent mitophagy regulation, and mitophagy impairment in the pathology of AD. We further discuss different ROCK inhibitors (synthetic drugs, natural compounds, and gene therapy-based approaches) and examine their effects on trig-gering neuronal growth and neuroprotection in AD and other NDDs. This comprehensive overview of the role of ROCK in mitophagy inhibition provides a possible explanation for the significance of ROCK inhibitors in the therapeutic management of AD and other NDDs.

引用

页数：19

共 210 条

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