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Role of Glycosphingolipids and Therapeutic Perspectives on Alzheimer's Disease

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Alzheimer's disease (AD) is a devastating neurodegenerative disorder dividing into two forms, early onset familial and late onset sporadic forms. Early onset genetic cases (familial AD (FAD)) constitute about 10% of all AD cases. Heretofore, highly fibrillinogenic and pathological Aβ peptide formation is regarded as the fundamental molecular basis for this disorder. Recent enormous efforts to find out a pathogenesis, however, have revealed that this disorder has a multiplicity of causes such as glycosphingolipids abnormalities, impairment of neurotrophin signaling, protein trafficking, and protein turnover. Most of these aspects were disclosed by the studies on FAD-related presenilin. In this review, we will focus on the current knowledge of many abnormal aspects of cellular lipids, especially glycosphingolipids other than a pathogenic Aβ production caused by the mutant presenilins as a model system. Moreover, we will discuss how these glycosphingolipids abnormalities cause the pathological conditions found in this disorder.

Keywords: Glycosphingolipids; Trk; cholesterol; familial Alzheimer's disease; ganglioside; lipid rafts; neurotrophin; presenilin

Document Type: Research Article


Affiliations: Department of Neurology, Fujita Health University School of Medicine, 1-98 Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.

Publication date: August 1, 2006

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  • CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in neurological and CNS disorders. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.

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