Next Generation Precision Medicine: CRISPR-mediated Genome Editing for the Treatment of Neurodegenerative Disorders

被引:21
作者
Raikwar, Sudhanshu P. [1 ,2 ]
Kikkeri, Nidhi S. [1 ]
Sakuru, Ragha [1 ]
Saeed, Daniyal [1 ]
Zahoor, Haris [1 ]
Premkumar, Keerthivaas [1 ]
Mentor, Shireen [1 ,3 ]
Thangavel, Ramasamy [1 ,2 ]
Dubova, Iuliia [1 ,2 ]
Ahmed, Mohammad Ejaz [1 ,2 ]
Selvakumar, Govindhasamy P. [1 ,2 ]
Kempuraj, Duraisamy [1 ,2 ]
Zaheer, Smita [1 ]
Iyer, Shankar S. [1 ,2 ]
Zaheer, Asgar [1 ,2 ]
机构
[1] Univ Missouri, Ctr Translat Neurosci, Sch Med, Dept Neurol, M741A Med Sci Bldg,1 Hosp Dr, Columbia, MO 65211 USA
[2] Harry S Truman Mem Vet Hosp, US Dept Vet Affairs, Columbia, MO 65201 USA
[3] Univ Western Cape, Dept Med Biosci, ZA-7535 Bellville, South Africa
基金
美国国家卫生研究院;
关键词
Alzheimer's disease; Amyotrophic lateral sclerosis; CRISPR; Frontotemporal dementia; genome editing; Huntington's disease; neuroinflammation; neurodegeneration; Parkinson's disease; GLIA MATURATION FACTOR; CONTROL CELL-LINE; IN-UTERO ELECTROPORATION; AMYLOID-BETA DEPOSITION; IPSC-DERIVED NEURONS; ALZHEIMERS-DISEASE; FRONTOTEMPORAL DEMENTIA; GAMMA-SECRETASE; GENE-EXPRESSION; MOUSE MODELS;
D O I
10.1007/s11481-019-09849-y
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Despite significant advancements in the field of molecular neurobiology especially neuroinflammation and neurodegeneration, the highly complex molecular mechanisms underlying neurodegenerative diseases remain elusive. As a result, the development of the next generation neurotherapeutics has experienced a considerable lag phase. Recent advancements in the field of genome editing offer a new template for dissecting the precise molecular pathways underlying the complex neurodegenerative disorders. We believe that the innovative genome and transcriptome editing strategies offer an excellent opportunity to decipher novel therapeutic targets, develop novel neurodegenerative disease models, develop neuroimaging modalities, develop next-generation diagnostics as well as develop patient-specific precision-targeted personalized therapies to effectively treat neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, Frontotemporal dementia etc. Here, we review the latest developments in the field of CRISPR-mediated genome editing and provide unbiased futuristic insights regarding its translational potential to improve the treatment outcomes andminimize financial burden. However, despite significant advancements, we would caution the scientific community that since the CRISPR field is still evolving, currently we do not know the full spectrum of CRISPR-mediated side effects. In the wake of the recent news regarding CRISPR-edited human babies being born in China, we urge the scientific community to maintain high scientific and ethical standards and utilize CRISPR for developing in vitro disease in a dish model, in vivo testing in nonhuman primates and lower vertebrates and for the development of neurotherapeutics for the currently incurable neurodegenerative disorders.
引用
收藏
页码:608 / 641
页数:34
相关论文
共 318 条
[111]   Glia Maturation Factor Induces Interleukin-33 Release from Astrocytes: Implications for Neurodegenerative Diseases [J].
Kempuraj, Duraisamy ;
Khan, Mohammad Moshahid ;
Thangavel, Ramasamy ;
Xiong, Zhi ;
Yang, Evert ;
Zaheer, Asgar .
JOURNAL OF NEUROIMMUNE PHARMACOLOGY, 2013, 8 (03) :643-650
[112]   SUPPRESSION OF GLIA MATURATION FACTOR EXPRESSION PREVENTS 1-METHYL-4-PHENYLPYRIDINIUM (MPP+)-INDUCED LOSS OF MESENCEPHALIC DOPAMINERGIC NEURONS [J].
Khan, M. M. ;
Zaheer, S. ;
Nehman, J. ;
Zaheer, A. .
NEUROSCIENCE, 2014, 277 :196-205
[113]   Absence of Glia Maturation Factor Protects Dopaminergic Neurons and Improves Motor Behavior in Mouse Model of Parkinsonism [J].
Khan, Mohammad Moshahid ;
Zaheer, Smita ;
Thangavel, Ramasamy ;
Patel, Margi ;
Kempuraj, Duraisamy ;
Zaheer, Asgar .
NEUROCHEMICAL RESEARCH, 2015, 40 (05) :980-990
[114]   Glia Maturation Factor Deficiency Suppresses 1-Methyl-4-Phenylpyridinium-Induced Oxidative Stress in Astrocytes [J].
Khan, Mohammad Moshahid ;
Kempuraj, Duraisamy ;
Zaheer, Smita ;
Zaheer, Asgar .
JOURNAL OF MOLECULAR NEUROSCIENCE, 2014, 53 (04) :590-599
[115]   Implicating Receptor Activator of NF-κB (RANK)/RANK Ligand Signalling in Microglial Responses to Toll-Like Receptor Stimuli [J].
Kichev, Anton ;
Eede, Pascale ;
Gressens, Pierre ;
Thornton, Claire ;
Hagberg, Henrik .
DEVELOPMENTAL NEUROSCIENCE, 2017, 39 (1-4) :192-206
[116]   In vivo genome editing with a small Cas9 orthologue derived from Campylobacter jejuni [J].
Kim, Eunji ;
Koo, Taeyoung ;
Park, Sung Wook ;
Kim, Daesik ;
Kim, Kyoungmi ;
Cho, Hee-Yeon ;
Song, Dong Woo ;
Lee, Kyu Jun ;
Jung, Min Hee ;
Kim, Seokjoong ;
Kim, Jin Hyoung ;
Kim, Jeong Hun ;
Kim, Jin-Soo .
NATURE COMMUNICATIONS, 2017, 8
[117]  
Kim ST, 2018, NAT METHODS, V15, P239, DOI [10.1038/nmeth.4554, 10.1038/NMETH.4554]
[118]   GBA1 deficiency negatively affects physiological α-synuclein tetramers and related multimers [J].
Kim, Sangjune ;
Yun, Seung Pil ;
Lee, Saebom ;
Umanah, George Essien ;
Bandaru, Veera Venkata Ratnam ;
Yin, Xiling ;
Rhee, Peter ;
Karuppagounder, Senthilkumar S. ;
Kwon, Seung-Hwan ;
Lee, Hojae ;
Mao, Xiaobo ;
Kim, Donghoon ;
Pandey, Akhilesh ;
Lee, Gabsang ;
Dawson, Valina L. ;
Dawson, Ted M. ;
Ko, Han Seok .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2018, 115 (04) :798-803
[119]   Highly efficient RNA-guided genome editing in human cells via delivery of purified Cas9 ribonucleoproteins [J].
Kim, Sojung ;
Kim, Daesik ;
Cho, Seung Woo ;
Kim, Jungeun ;
Kim, Jin-Soo .
GENOME RESEARCH, 2014, 24 (06) :1012-1019
[120]   The FTD-like syndrome causing TREM2 T66M mutation impairs microglia function, brain perfusion, and glucose metabolism [J].
Kleinberger, Gernot ;
Brendel, Matthias ;
Mracsko, Eva ;
Wefers, Benedikt ;
Groeneweg, Linda ;
Xiang, Xianyuan ;
Focke, Carola ;
Deussing, Maximilian ;
Suarez-Calvet, Marc ;
Mazaheri, Fargol ;
Parhizkar, Samira ;
Pettkus, Nadine ;
Wurst, Wolfgang ;
Feederle, Regina ;
Bartenstein, Peter ;
Mueggler, Thomas ;
Arzberger, Thomas ;
Knuesel, Irene ;
Rominger, Axel ;
Haass, Christian .
EMBO JOURNAL, 2017, 36 (13) :1837-1853