Role of SUMOylation in Neurodegenerative Diseases

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2022 Nov 11

PMID 36359791

Authors

Nicolas Mandel

Nitin Agarwal

Affiliations

Soon will be listed here.

Abstract

Neurodegenerative diseases (NDDs) are irreversible, progressive diseases with no effective treatment. The hallmark of NDDs is the aggregation of misfolded, modified proteins, which impair neuronal vulnerability and cause brain damage. The loss of synaptic connection and the progressive loss of neurons result in cognitive defects. Several dysregulated proteins and overlapping molecular mechanisms contribute to the pathophysiology of NDDs. Post-translational modifications (PTMs) are essential regulators of protein function, trafficking, and maintaining neuronal hemostasis. The conjugation of a small ubiquitin-like modifier (SUMO) is a reversible, dynamic PTM required for synaptic and cognitive function. The onset and progression of neurodegenerative diseases are associated with aberrant SUMOylation. In this review, we have summarized the role of SUMOylation in regulating critical proteins involved in the onset and progression of several NDDs.

Citing Articles

Site-specific protein SUMOylation translational incorporation of a proximity-reactive pyrrolysine analogue.

Chan Y, Lee M, Chan M RSC Chem Biol. 2025; 6(3):358-363.

PMID: 39911855 PMC: 11791516. DOI: 10.1039/d4cb00135d.

Comprehensive review on Alzheimer's disease: From the posttranslational modifications of Tau to corresponding treatments.

Li X, Ba Z, Huang J, Chen J, Jiang J, Huang N Ibrain. 2024; 10(4):427-438.

PMID: 39691421 PMC: 11649392. DOI: 10.1002/ibra.12176.

Interpretable multimodal machine learning (IMML) framework reveals pathological signatures of distal sensorimotor polyneuropathy.

Nguyen P, Garger D, Lu D, Maalmi H, Prokisch H, Thorand B Commun Med (Lond). 2024; 4(1):265.

PMID: 39681608 PMC: 11649904. DOI: 10.1038/s43856-024-00637-1.

SENP7 inhibits glioblastoma metastasis and invasion by dissociating SUMO2/3 binding to specific target proteins.

Zhang J, Zheng H, Liang P Open Med (Wars). 2024; 19(1):20241052.

PMID: 39381427 PMC: 11459272. DOI: 10.1515/med-2024-1052.

SUMOylation at the crossroads of gut health: insights into physiology and pathology.

Ma X, Li M, Qi G, Wei L, Zhang D Cell Commun Signal. 2024; 22(1):404.

PMID: 39160548 PMC: 11331756. DOI: 10.1186/s12964-024-01786-5.

References

Lashuel H, Overk C, Oueslati A, Masliah E . The many faces of α-synuclein: from structure and toxicity to therapeutic target. Nat Rev Neurosci. 2012; 14(1):38-48. PMC: 4295774. DOI: 10.1038/nrn3406. View

Ruffmann C, Zini M, Goldwurm S, Bramerio M, Spinello S, Rusconi D . Lewy body pathology and typical Parkinson disease in a patient with a heterozygous (R275W) mutation in the Parkin gene (PARK2). Acta Neuropathol. 2012; 123(6):901-3. DOI: 10.1007/s00401-012-0991-7. View

Song W, Chen J, Petrilli A, Liot G, Klinglmayr E, Zhou Y . Mutant huntingtin binds the mitochondrial fission GTPase dynamin-related protein-1 and increases its enzymatic activity. Nat Med. 2011; 17(3):377-82. PMC: 3051025. DOI: 10.1038/nm.2313. View

Dugger B, Dickson D . Pathology of Neurodegenerative Diseases. Cold Spring Harb Perspect Biol. 2017; 9(7). PMC: 5495060. DOI: 10.1101/cshperspect.a028035. View

Stankovic-Valentin N, Drzewicka K, Konig C, Schiebel E, Melchior F . Redox regulation of SUMO enzymes is required for ATM activity and survival in oxidative stress. EMBO J. 2016; 35(12):1312-29. PMC: 4867669. DOI: 10.15252/embj.201593404. View

Braschi E, Zunino R, McBride H . MAPL is a new mitochondrial SUMO E3 ligase that regulates mitochondrial fission. EMBO Rep. 2009; 10(7):748-54. PMC: 2727426. DOI: 10.1038/embor.2009.86. View

Hochstrasser M . SP-RING for SUMO: new functions bloom for a ubiquitin-like protein. Cell. 2001; 107(1):5-8. DOI: 10.1016/s0092-8674(01)00519-0. View

Dawson T, Dawson V . The role of parkin in familial and sporadic Parkinson's disease. Mov Disord. 2010; 25 Suppl 1:S32-9. PMC: 4115293. DOI: 10.1002/mds.22798. View

Bonifati V, Rizzu P, van Baren M, Schaap O, Breedveld G, Krieger E . Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism. Science. 2002; 299(5604):256-9. DOI: 10.1126/science.1077209. View

10.

Abeywardana T, Pratt M . Extent of inhibition of α-synuclein aggregation in vitro by SUMOylation is conjugation site- and SUMO isoform-selective. Biochemistry. 2015; 54(4):959-61. DOI: 10.1021/bi501512m. View

11.

Morita Y, Kanei-Ishii C, Nomura T, Ishii S . TRAF7 sequesters c-Myb to the cytoplasm by stimulating its sumoylation. Mol Biol Cell. 2005; 16(11):5433-44. PMC: 1266438. DOI: 10.1091/mbc.e05-08-0731. View

12.

Repici M, Giorgini F . DJ-1 in Parkinson's Disease: Clinical Insights and Therapeutic Perspectives. J Clin Med. 2019; 8(9). PMC: 6780414. DOI: 10.3390/jcm8091377. View

13.

Rangel Rojas D, Kuner R, Agarwal N . Metabolomic signature of type 1 diabetes-induced sensory loss and nerve damage in diabetic neuropathy. J Mol Med (Berl). 2019; 97(6):845-854. DOI: 10.1007/s00109-019-01781-1. View

14.

Paleologou K, Oueslati A, Shakked G, Rospigliosi C, Kim H, Lamberto G . Phosphorylation at S87 is enhanced in synucleinopathies, inhibits alpha-synuclein oligomerization, and influences synuclein-membrane interactions. J Neurosci. 2010; 30(9):3184-98. PMC: 2947449. DOI: 10.1523/JNEUROSCI.5922-09.2010. View

15.

Pelisch F, Gerez J, Druker J, Schor I, Munoz M, Risso G . The serine/arginine-rich protein SF2/ASF regulates protein sumoylation. Proc Natl Acad Sci U S A. 2010; 107(37):16119-24. PMC: 2941313. DOI: 10.1073/pnas.1004653107. View

16.

Schorova L, Martin S . Sumoylation in Synaptic Function and Dysfunction. Front Synaptic Neurosci. 2016; 8:9. PMC: 4848311. DOI: 10.3389/fnsyn.2016.00009. View

17.

Johnson E . Protein modification by SUMO. Annu Rev Biochem. 2004; 73:355-82. DOI: 10.1146/annurev.biochem.73.011303.074118. View

18.

Baczyk D, Audette M, Drewlo S, Levytska K, Kingdom J . SUMO-4: A novel functional candidate in the human placental protein SUMOylation machinery. PLoS One. 2017; 12(5):e0178056. PMC: 5435238. DOI: 10.1371/journal.pone.0178056. View

19.

Hoppe J, Salbego C, Cimarosti H . SUMOylation: Novel Neuroprotective Approach for Alzheimer's Disease?. Aging Dis. 2015; 6(5):322-30. PMC: 4567215. DOI: 10.14336/AD.2014.1205. View

20.

Soares E, de Souza A, Zanella C, Carmichael R, Henley J, Wilkinson K . Effects of amyloid-β on protein SUMOylation and levels of mitochondrial proteins in primary cortical neurons. IBRO Neurosci Rep. 2022; 12:142-148. PMC: 9210492. DOI: 10.1016/j.ibneur.2022.01.003. View