SGTA associates with intracellular aggregates in neurodegenerative diseases.

Abstract

Intracellular aggregates are a common pathological hallmark of neurodegenerative diseases such as polyglutamine (polyQ) diseases, amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and multiple system atrophy (MSA). Aggregates are mainly formed by aberrant disease-specific proteins and are accompanied by accumulation of other aggregate-interacting proteins. Although aggregate-interacting proteins have been considered to modulate the formation of aggregates and to be involved in molecular mechanisms of disease progression, the components of aggregate-interacting proteins remain unknown. In this study, we showed that small glutamine-rich tetratricopeptide repeat-containing protein alfa (SGTA) is an aggregate-interacting protein in neurodegenerative diseases. Immunohistochemistry showed that SGTA interacted with intracellular aggregates in Huntington disease (HD) cell models and neurons of HD model mice. We also revealed that SGTA colocalized with intracellular aggregates in postmortem brains of patients with polyQ diseases including spinocerebellar ataxia (SCA)1, SCA2, SCA3, and dentatorubral-pallidoluysian atrophy. In addition, SGTA colocalized with glial cytoplasmic inclusions in the brains of MSA patients, whereas no accumulation of SGTA was observed in neurons of PD and ALS patients. In vitro study showed that SGTA bound to polyQ aggregates through its C-terminal domain and SGTA overexpression reduced intracellular aggregates. These results suggest that SGTA may play a role in the formation of aggregates and may act as potential modifier of molecular pathological mechanisms of polyQ diseases and MSA.

• Authors: Shun Kubota, Hiroshi Doi, Shigeru Koyano, Kenichi Tanaka, Hiroyasu Komiya, Atsuko Katsumoto, Shingo Ikeda, Shunta Hashiguchi, Haruko Nakamura, Ryoko Fukai, Keita Takahashi, Misako Kunii, Mikiko Tada, Hideyuki Takeuchi, Fumiaki Tanaka
• Journal: Molecular brain (Mol Brain) Vol. 14 Issue 1 Pg. 59 (03 23 2021) ISSN: 1756-6606 [Electronic] England
• PMID: 33757575 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• HTT protein, human
• Huntingtin Protein
• Molecular Chaperones
• Nerve Tissue Proteins
• Peptide Fragments
• Peptides
• Protein Aggregates
• Recombinant Proteins
• SGTA protein, human
• Sgta protein, mouse
• alpha-Synuclein
• polyglutamine

Topics

• Animals
• Autopsy
• Brain (pathology)
• Brain Chemistry
• Cell Line, Tumor
• Humans
• Huntingtin Protein (genetics, metabolism)
• Inclusion Bodies (chemistry)
• Mice
• Mice, Transgenic
• Molecular Chaperones (metabolism)
• Nerve Tissue Proteins (metabolism)
• Neuroblastoma
• Neurodegenerative Diseases (metabolism, pathology)
• Peptide Fragments (genetics, metabolism)
• Peptides (metabolism)
• Protein Aggregates
• Protein Aggregation, Pathological (metabolism)
• Recombinant Proteins (metabolism)
• Solubility
• Subcellular Fractions (metabolism)
• Transfection
• alpha-Synuclein (analysis)