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Disorders of cholesterol metabolism and their unanticipated convergent mechanisms of disease.

ABSTRACT: Cholesterol plays a key role in many cellular processes, and is generated by cells through de novo biosynthesis or acquired from exogenous sources through the uptake of low-density lipoproteins. Cholesterol biosynthesis is a complex, multienzyme-catalyzed pathway involving a series of sequentially acting enzymes. Inherited defects in genes encoding cholesterol biosynthetic enzymes or other regulators of cholesterol homeostasis result in severe metabolic diseases, many of which are rare in the general population and currently without effective therapy. Historically, these diseases have been viewed as discrete disorders, each with its own genetic cause and distinct pathogenic cascades that lead to its specific clinical features. However, studies have recently shown that three of these diseases have an unanticipated mechanistic convergence. This surprising finding is not only shedding light on details of cellular cholesterol homeostasis but also suggesting novel approaches to therapy.

SUBMITTER: Platt FM

PROVIDER: S-EPMC6292211 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Disorders of cholesterol metabolism and their unanticipated convergent mechanisms of disease.

Platt Frances M FM Wassif Christopher C Colaco Alexandria A Dardis Andrea A Lloyd-Evans Emyr E Bembi Bruno B Porter Forbes D FD

Annual review of genomics and human genetics 20140101

Cholesterol plays a key role in many cellular processes, and is generated by cells through de novo biosynthesis or acquired from exogenous sources through the uptake of low-density lipoproteins. Cholesterol biosynthesis is a complex, multienzyme-catalyzed pathway involving a series of sequentially acting enzymes. Inherited defects in genes encoding cholesterol biosynthetic enzymes or other regulators of cholesterol homeostasis result in severe metabolic diseases, many of which are rare in the ge ...[more]

PMID: 25184529

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Dataset Information

Disorders of cholesterol metabolism and their unanticipated convergent mechanisms of disease.

Publications

Disorders of cholesterol metabolism and their unanticipated convergent mechanisms of disease.

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