Niemann-Pick Disease Type C (NPDC) by Mutation of <i>NPC1</i> and <i>NPC2</i>: Aberrant Lysosomal Cholesterol Trafficking and Oxidative Stress

Abstract

Cholesterol trafficking is initiated by the endocytic pathway and transported from endo/lysosomes to other intracellular organelles. Deficiencies in cholesterol-sensing and binding proteins NPC1 and NPC2 induce accumulation in lysosomes and the malfunction of trafficking to other organelles. Each organelle possesses regulatory factors to induce cholesterol trafficking. The mutation of NPC1 and NPC2 genes induces Niemann-Pick disease type C (NPDC), which is a hereditary disease and causes progressive neurodegeneration, developmental disability, hypotonia, and ataxia. Oxidative stress induces damage in NPDC-related intracellular organelles. Although studies on the relationship between NPDC and oxidation are relatively rare, several studies have reported the therapeutic potential of antioxidants in treating NPDC. Investigating antioxidant drugs to relieve oxidative stress and cholesterol accumulation is suggested to be a powerful tool for developing treatments for NPDC. Understanding NPDC provides challenging issues in understanding the oxidative stress–lysosome metabolism of the lipid axis. Thus, we elucidated the relationship between complexes of intracellular organelles and NPDC to develop our knowledge and suggested potential antioxidant reagents for NPDC therapy.

Keywords

• cholesterol trafficking
• Niemann-Pick disease type C
• lysosomal storage disorders
• lysosomal proteins
• oxidative stress