Molecular Aspects of Neurodegeneration and Neuroprotection

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Neurodegenerative diseases are a complex heterogeneous group of diseases associated with site-specific premature and slow death of certain neuronal populations in brain and spinal cord tissues. For ...
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Kainic Acid-Mediated Neural Cell Death in Brain: Interplay Among Glycerophospholipid-, Sphingolipid-, and Cholesterol-Derived Lipid Mediators

Pp. 39-49 (11)

Wei-Yi Ong and Akhlaq A. Farooqui

Abstract

In addition to integral proteins, neural membranes are composed of glycerophospholipids, sphingolipids, and cholesterol, which provide membranes with structural integrity (suitable stability, fluidity, and permeability). Kainic acid (KA), an excitotoxin, markedly upregulates glycerophospholipids, sphingolipids, and cholesterol metabolism resulting not only in loss of essential lipids and inducing changes in neural membrane fluidity and permeability, but also in elevations in glycerophospholipid, sphingolipid, and cholesterol-derived lipid mediators. These processes result in depolarization, sustained increase in Ca2+ and stimulation of Ca2+-dependent enzymes including PLA2, PLC, nitric oxide synthase, calpains, and endonucleases. Sustained stimulation of these enzymes, generation, and interplay among glycerophospholipid-, sphingolipid-, and cholesterol-derived lipid mediators along with mitochondrial dysfunction, decrease in ATP levels, changes in redox status of neural cell may be responsible for neurodegeneration through apoptosis and necrosis in KA-mediated neurotoxicity. Other KAmediated neurochemical changes include synaptic reorganization associated with recapitulation of hippocampal development and synaptogenesis following KA-induced seizures.

Keywords:

Lipid mediators; kainic acid-mediated neurotoxicity; glycerophospholipids, sphingolipids, cholesterol; mitochondrial dysfunction

Affiliation:

Department of Anatomy, National University of Singapore, Singapore 119260.