Molecular Mechanisms and Therapeutics for Spinocerebellar Ataxia Type 2

  • Polina A. Egorova
  • Ilya B. BezprozvannyEmail author


The effective therapeutic treatment and the disease-modifying therapy for spinocerebellar ataxia type 2 (SCA2) (a progressive hereditary disease caused by an expansion of polyglutamine in the ataxin-2 protein) is not available yet. At present, only symptomatic treatment and methods of palliative care are prescribed to the patients. Many attempts were made to study the physiological, molecular, and biochemical changes in SCA2 patients and in a variety of the model systems to find new therapeutic targets for SCA2 treatment. A better understanding of the uncovered molecular mechanisms of the disease allowed the scientific community to develop strategies of potential therapy and helped to create some promising therapeutic approaches for SCA2 treatment. Recent progress in this field will be discussed in this review article.

Key Words

Spinocerebellar ataxia type 2 polyglutamine disorders cerebellum calcium signaling aggregation. 



Autosomal dominant cerebellar ataxia


Action potential


Antisense oligonucleotide


Bacterial artificial chromosome

BK channel

Large-conductance calcium-activated potassium channel


Binucleated cell


Cyclin-dependent kinase 5


Climbing fiber


C-terminal constitutive Hsc70-interacting protein




Complex spike




Diffusion-tensor imaging




Evoked potential


Endoplasmic reticulum


Huntington’s disease


Heat shock protein




IP3-induced calcium release


Induced pluripotent stem cells


Inositol 1,4,5-trisphosphate receptor






Long-term depression


Mossy fiber


Metabotropic glutamate receptor


Micronuclei formation


Magnetic resonance imaging


Messenger RNA


Mesenchymal stem cells


Poly(A)-binding protein


Purkinje cell


Purkinje cell protein 2


Parkinson’s disease


Parallel fiber


Protein kinase C


Periodic leg movement




Post-translational modifications


PolyQ-binding protein 1


Rapid eye movement


Retinoid-related orphan receptor α


Ryanodine receptor


Scale for the Assessment and Rating of Ataxia


Spinocerebellar ataxia


Spinocerebellar ataxia type 2


Stress granules

SK channel

Small-conductance calcium-activated potassium channel


Superoxide dismutase


Transient receptor potential canonical 3


Voxel-based morphometry


Voltage-dependent calcium channels


Wild type





Ilya B. Bezprozvanny is a holder of the Carl J. and Hortense M. Thomsen Chair in Alzheimer’s Disease Research. This work was supported by the National Institutes of Health Grant R01NS056224 (Ilya B. Bezprozvanny), Russian State Grant 17.991.2017/4.6 (Ilya B. Bezprozvanny), Russian Science Foundation Grant 18-75-00025 (Polina A. Egorova), Presidential Grant МК-1299.2019.4 (Polina A. Egorova), and Russian Science Foundation Grant 19-15-00184 (Ilya B. Bezprozvanny). The financial support was divided in the following way: research work related to Figure 1 was supported by the Russian State Grant 17.991.2017/4.6, research work related to Figure 2 was supported by the Presidential Grant МК-1299.2019.4, research work related to Figure 3 was supported by the Russian Science Foundation Grant 18-75-00025, and research work related to Figure 4 was supported by the Russian Science Foundation Grant 19-15-00184.


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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2019

Authors and Affiliations

  1. 1.Laboratory of Molecular NeurodegenerationPeter the Great St.Petersburg Polytechnic UniversitySt. PetersburgRussia
  2. 2.Department of PhysiologyUniversity of Texas Southwestern Medical CenterDallasUSA

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