Neuropathology of spinocerebellar ataxia type 3 (SCA3) – Machado-Joseph disease




Neurology; Clinical condition; Treatment; Quality of life.


Spinocerebellar ataxia type 3, also known as Machado-Joseph disease, is an autosomal dominant neurodegenerative disorder, caused by an expansion of the CAG repeat that encodes glutamine in the ATXN3 gene. It affects both men and women, with symptoms that are usually late, appearing around the second decade of life and worsening with advancing age. Although rare, it is the most common form of spinocerebellar ataxia and there is no evidence of therapies capable of promoting a cure. Thus, the present study gathered information to update knowledge about this disease. This is an integrative literature review carried out in the PUBMED, SciELO and BVS databases. Progressive cerebellar ataxia is common in these patients. In the clinical spectrum it includes oculomotor abnormalities, sleep disorders, pyramidal syndrome, extrapyramidal signs and peripheral neuropathy. These neurological symptoms are expressed by the effect of neuronal loss in specific regions of the cerebellum, basal ganglia, brain stem and spinal cord. Anxiety, depression and a high level of fatigue can occur. There is still no effective treatment that can change the natural course of this disease. The most recent studies have the therapeutic target of gene silencing and the interception of toxic effects caused by the proteins produced. Symptomatic therapies and physical therapy have been performed to improve quality of life. Knowing the clinical characteristics of Machado-Joseph disease, which is a serious, incurable, highly debilitating condition and capable of generating a high burden of suffering in its patients, is important in the performance of the neurologist.


Dantuma, N. P., & Herzog, L. K. (2020). Machado-Joseph Disease: A Stress Combating Deubiquitylating Enzyme Changing Sides. Advances in experimental medicine and biology, 1233, 237–260.

de Mattos, E. P., Kolbe Musskopf, M., Bielefeldt Leotti, V., Saraiva-Pereira, M. L., & Jardim, L. B. (2019). Genetic risk factors for modulation of age at onset in Machado-Joseph disease/spinocerebellar ataxia type 3: a systematic review and meta-analysis. Journal of neurology, neurosurgery, and psychiatry, 90(2), 203–210.

Duarte-Silva S, & Maciel P. (2018). Pharmacological Therapies for Machado-Joseph Disease. Advances in Experimental Medicine and Biology. 1049:369-394. DOI: 10.1007/978-3-319-71779-1_19.

Hou, X., Gong, X., Zhang, L., Li, T., Yuan, H., Xie, Y., Peng, Y., Qiu, R., Xia, K., Tang, B., & Jiang, H. (2019). Identification of a potential exosomal biomarker in spinocerebellar ataxia Type 3/Machado-Joseph disease. Epigenomics, 11(9), 1037–1056.

Klockgether T, Mariotti C, & Paulson HL. (2019). Spinocerebellar ataxia. Nature reviews. Disease Primers. 5(1):24. DOI: 10.1038/s41572-019-0074-3.

Koeppen A. H. (2018). The Neuropathology of Spinocerebellar Ataxia Type 3/Machado-Joseph Disease. Advances in experimental medicine and biology, 1049, 233–241.

Lima, M., & Raposo, M. (2018). Towards the Identification of Molecular Biomarkers of Spinocerebellar Ataxia Type 3 (SCA3)/Machado-Joseph Disease (MJD). Advances in experimental medicine and biology, 1049, 309–319.

Lin, M. T., Yang, J. S., Chen, P. P., Qian, M. Z., Lin, H. X., Chen, X. P., Shang, X. J., Wang, D. N., Chen, Y. C., Jiang, B., Chen, Y. J., Chen, W. J., Wang, N., & Gan, S. R. (2018). Bidirectional Connections between Depression and Ataxia Severity in Spinocerebellar Ataxia Type 3 Patients. European neurology, 79(5-6), 266–271.

Marques, Thames dos Santos, Furia, Cristina Lemos Barbosa, & Lira, Juliana Onofre de. (2020). Atuação fonoaudiológica na doença de Machado-Joseph: relato de caso. Audiology - Communication Research, 25, e2264. Epub May 22, 2020.

Matos, C. A., de Almeida, L. P., & Nóbrega, C. (2019). Machado-Joseph disease/spinocerebellar ataxia type 3: lessons from disease pathogenesis and clues into therapy. Journal of neurochemistry, 148(1), 8–28.

Mendonça, N., França, M. C., Jr, Gonçalves, A. F., & Januário, C. (2018). Clinical Features of Machado-Joseph Disease. Advances in experimental medicine and biology, 1049, 255–273.

Rezende, T., de Paiva, J., Martinez, A., Lopes-Cendes, I., Pedroso, J. L., Barsottini, O., Cendes, F., & França, M. C., Jr (2018). Structural signature of SCA3: From presymptomatic to late disease stages. Annals of neurology, 84(3), 401–408.

Saute, J., & Jardim, L. B. (2018). Planning Future Clinical Trials for Machado-Joseph Disease. Advances in experimental medicine and biology, 1049, 321–348.

Soong, B. W., & Morrison, P. J. (2018). Spinocerebellar ataxias. Handbook of clinical neurology, 155, 143–174.

Souza F de J, Oliveira HG de, Marreiro J dos S, & Miguel MMMC. (2018). A abordagem fisioterapêutica na marcha da doença Machado Joseph. Rev Inic Cient Ext;1(Esp):148-54.

Yang, J. S., Xu, H. L., Chen, P. P., Sikandar, A., Qian, M. Z., Lin, H. X., Lin, M. T., Chen, W. J., Wang, N., Wu, H., & Gan, S. R. (2020). Ataxic Severity Is Positively Correlated With Fatigue in Spinocerebellar Ataxia Type 3 Patients. Frontiers in neurology, 11, 266.

Yuan, X., Ou, R., Hou, Y., Chen, X., Cao, B., Hu, X., & Shang, H. (2019). Extra-Cerebellar Signs and Non-motor Features in Chinese Patients With Spinocerebellar Ataxia Type 3. Frontiers in neurology, 10, 110.



How to Cite

VAZ, R. L. .; RIBEIRO, G. R. .; NERY, L. G. .; COSTA, A. C. M. M. da; OLIVEIRA, G. S. .; ARRUDA, J. T. Neuropathology of spinocerebellar ataxia type 3 (SCA3) – Machado-Joseph disease. Research, Society and Development, [S. l.], v. 10, n. 3, p. e16910313138, 2021. DOI: 10.33448/rsd-v10i3.13138. Disponível em: Acesso em: 26 mar. 2023.



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