Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0007758 (cerebellar ataxia)
 3,609 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder characterized by cerebellar ataxia and oculocutaneous telangiectasias. The gene mutated in this disease, Atm (A-T mutated), encodes a serine/threonine protein kinase that has been traditionally considered to be a nuclear protein controlling cell-cycle progression. However, many of the growth abnormalities observed in patients with A-T, including neuronal degeneration and insulin resistance, remain difficult to explain with nuclear localization of ATM. Here, recent advances in elucidating the cytoplasmic localization and function of ATM are reviewed. Particular attention is given to the role of ATM in insulin signaling and Akt activation. The potential for cytoplasmic ATM protein kinase to be an emerging therapeutic target for treating diabetes, cancer and neuronal degeneration is discussed.
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PMID:Cytoplasmic ATM protein kinase: an emerging therapeutic target for diabetes, cancer and neuronal degeneration. 2131 78

Ataxia-telangiectasia (A-T) is an autosomal recessive primary immunodeficiency (PID) disease that is caused by mutations in ataxia-telangiectasia mutated (ATM) gene encoding a serine/threonine protein kinase. A-T patients represent a broad range of clinical manifestations including progressive cerebellar ataxia, oculocutaneous telangiectasia, variable immunodeficiency, radiosensitivity, susceptibility to malignancies, and increased metabolic diseases. This congenital disorder has phenotypic heterogeneity, and the severity of symptoms varies in different patients based on severity of mutations and disease progression. The principal role of nuclear ATM is the coordination of cellular signaling pathways in response to DNA double-strand breaks, oxidative stress, and cell cycle checkpoint. The pathogenesis of A-T is not limited to the role of ATM in the DNA damage response (DDR) pathway, and it has other functions mainly in the hematopoietic cells and neurons. ATM adjusts the functions of organelles such as mitochondria and peroxisomes and also regulates angiogenesis and glucose metabolisms. However, ATM has other functions in the cells (especially cell viability) that need further investigations. In this review, we described functions of ATM in the nucleus and cytoplasm, and also its association with some disorder formation such as neurologic, immunologic, vascular, pulmonary, metabolic, and dermatologic complications.
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PMID:Ataxia-telangiectasia: A review of clinical features and molecular pathology. 3068 76