| 摘要 |
Niemann-Pick type C2 (NP-C2) disease is a fatal lipid storage disorder characterized by massive lysosomal accumulation of cholesterol. The present invention identifies HE1 as the gene responsible for NP-C2. Treatment of NP-C2 fibroblasts with an exogenous HE1 genetic element ameliorated the cholesterol accumulation phenotype. HE1 functions in intracellular cholesterol transport. The present invention provides therapeutic compositions consisting of HE1 polynucleotide and polypeptide sequences, as well as an expression system for expressing HE1 in target cells. These therapeutic compositions can be used to target diseases involving faulty cholesterol transport and regulation, including NP-C2, atherosclerosis, Alzheimer's, diabetes, and cardiovascular disease. In addition, the present invention provides methods of diagnosing both NP-C2 and the ability of a subject to genetically transmit the disease by detecting mutations in the HE1 gene sequence. |
