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1.
Physiol Res ; 73(2): 189-203, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38710051

ABSTRACT

This comprehensive review explores the physiological and pathophysiological significance of VPS13A, a protein encoded by the VPS13A gene. The VPS13A gene is associated with Chorea-acanthocytosis (ChAc), a rare hereditary neurodegenerative disorder. The review covers essential aspects, beginning with the genetics of VPS13A, highlighting its role in the pathogenesis of ChAc, and addressing the spectrum of genetic variants involved. It delves into the structure and function of the VPS13A protein, emphasizing its presence in various tissues and its potential involvement in protein trafficking and lipid homeostasis. Molecular functions of VPS13A in the brain tissue and other cell types or tissues with respect to their role in cytoskeletal regulation and autophagy are explored. Finally, it explores the intriguing link between VPS13A mutations, lipid imbalances, and neurodegeneration, shedding light on future research directions. Overall, this review serves as a comprehensive resource for understanding the pivotal role of VPS13A in health and disease, particularly in the context of ChAc. Key words: Chorein , Tumor, Actin, Microfilament, Gene expression, Chorea-acanthocytosis.


Subject(s)
Neuroacanthocytosis , Vesicular Transport Proteins , Humans , Animals , Vesicular Transport Proteins/metabolism , Vesicular Transport Proteins/genetics , Neuroacanthocytosis/metabolism , Neuroacanthocytosis/genetics , Neuroacanthocytosis/physiopathology , Neuroacanthocytosis/pathology , Mutation , Lipid Metabolism/physiology , Lipid Metabolism/genetics
2.
Hum Exp Toxicol ; 38(7): 762-774, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30943778

ABSTRACT

Androgenetic alopecia is the most common type of alopecia, and it affects humans of both genders. Finasteride is a type II selective 5α-reductase inhibitor that is administered orally to treat androgenetic alopecia and benign prostatic hyperplasia in human males. However, its effect on the vital organs of females is unknown. This study was designed to investigate the effects of finasteride on the vital organs such as liver, kidney, and heart of female mice. To study the prospective effects of finasteride, female mice were orally administered two doses of finasteride (0.5 and 1.5 mg/kg) once daily for 35 days, and serum levels of various biochemical parameters and histopathology of various organs were examined. The results showed that serum levels of alkaline phosphatase were significantly increased by both high- and low-dose finasteride, whereas cholesterol was significantly increased by the high dose only. Creatine kinase was significantly increased by the high and low doses, whereas glucose was significantly decreased by both doses. Histopathological analysis and DNA damage assays showed that finasteride has adverse effects within both the short and the long periods in female mice. In addition, the proapoptotic genes Bax and caspase-3 were significantly increased by high dose finasteride, whereas the antiapoptotic gene Bcl-2 was significantly decreased by the low and high doses. In conclusion, finasteride is not currently approved for therapeutic use in females, and the findings in this study suggest caution in any future consideration of such use.


Subject(s)
5-alpha Reductase Inhibitors/toxicity , Finasteride/toxicity , Alkaline Phosphatase/blood , Animals , Apoptosis/drug effects , Blood Glucose/analysis , Cholesterol/blood , Creatine Kinase/blood , DNA Damage , Female , Heart/drug effects , Kidney/drug effects , Kidney/pathology , Liver/drug effects , Liver/pathology , Lymphocytes/drug effects , Mice , Spleen/drug effects , Spleen/pathology
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