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Review
. 2023 Apr:86:101856.
doi: 10.1016/j.arr.2023.101856. Epub 2023 Jan 19.

Role of UCHL1 in the pathogenesis of neurodegenerative diseases and brain injury

Zhiping Mi  1 , Steven H Graham  2
Affiliations
Review

Role of UCHL1 in the pathogenesis of neurodegenerative diseases and brain injury

Zhiping Mi et al. Ageing Res Rev. 2023 Apr.

Abstract

UCHL1 is a multifunctional protein expressed at high concentrations in neurons in the brain and spinal cord. UCHL1 plays important roles in regulating the level of cellular free ubiquitin and redox state as well as the degradation of select proteins. This review focuses on the potential role of UCHL1 in the pathogenesis of neurodegenerative diseases and brain injury and recovery. Subjects addressed in the review include 1) Normal physiological functions of UCHL1. 2) Posttranslational modification sites and splice variants that alter the function of UCHL1 and mouse models with mutations and deletions of UCHL1. 3) The hypothesized role and pathogenic mechanisms of UCHL1 in neurodegenerative diseases and brain injury. 4) Potential therapeutic strategies targeting UCHL1 in these disorders.

Keywords: Brain injury; Neurodegeneration; Protein degradation; Ubiquitin C-terminal hydrolase 1; Ubiquitin-proteasome pathway.

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Conflict of interest statement

Conflict of interest The authors declare no conflict of interest. The contents do not represent the views of the Department of Veterans Affairs or the United States Government.

Figures

Figure 1.
Figure 1.
Potential mechanisms of UCHL1’s structural and functional impairment in neurodegeneration. Alterations in the structure and function of UCHL1 by genetic mutation, reactive lipid, NO and oxidation lead to neuronal cell death through disruption of UPP and ALP, increased cellular insolubility and oxidative stress.
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References

    1. Adams JH, Doyle D, Graham DI, Lawrence AE, McLellan DR, 1984. Diffuse axonal injury in head injuries caused by a fall. Lancet 2, 1420–1422. - PubMed
    1. Baba M, Nakajo S, Tu PH, Tomita T, Nakaya K, Lee VM, Trojanowski JQ, Iwatsubo T, 1998. Aggregation of alpha-synuclein in Lewy bodies of sporadic Parkinson’s disease and dementia with Lewy bodies. Am J Pathol 152, 879–884. - PMC - PubMed
    1. Ballarin B, Tymianski M, 2018. Discovery and development of NA-1 for the treatment of acute ischemic stroke. Acta Pharmacol Sin 39, 661–668. - PMC - PubMed
    1. Bheda A, Gullapalli A, Caplow M, Pagano JS, Shackelford J, 2010. Ubiquitin editing enzyme UCH L1 and microtubule dynamics: implication in mitosis. Cell cycle (Georgetown, Tex 9, 980–994. - PMC - PubMed
    1. Bilguvar K, Tyagi NK, Ozkara C, Tuysuz B, Bakircioglu M, Choi M, Delil S, Caglayan AO, Baranoski JF, Erturk O, Yalcinkaya C, Karacorlu M, Dincer A, Johnson MH, Mane S, Chandra SS, Louvi A, Boggon TJ, Lifton RP, Horwich AL, Gunel M, 2013. Recessive loss of function of the neuronal ubiquitin hydrolase UCHL1 leads to early-onset progressive neurodegeneration. Proc Natl Acad Sci U S A 110, 3489–3494. - PMC - PubMed

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