Glomerular pathology in Alport syndrome: a molecular perspective |
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Authors: | Dominic Cosgrove |
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Institution: | (1) Boys Town National Research Hospital, 555 No. 30th Street, Omaha, NE 68131, USA |
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Abstract: | We have known for some time that mutations in the genes encoding 3 of the 6 type IV collagen chains are the underlying defect
responsible for both X-linked (where the COL4A5 gene is involved) and autosomal (where either COL4A3 or COL4A4 genes are involved)
Alport syndrome. The result of these mutations is the absence of the sub-epithelial network of all three chains in the glomerular
basement membrane (GBM), resulting, at maturity, in a type IV collagen GBM network comprising only α1(IV) and α2(IV) chains.
The altered GBM functions adequately in early life. Eventually, there is onset of proteinuria associated with the classic
and progressive irregular thickening, thinning, and splitting of the GBM, which culminates in end-stage renal failure. We
have learned much about the molecular events associated with disease onset and progression through the study of animal models
for Alport syndrome, and have identified some potential therapeutic approaches that may serve to delay the onset or slow the
progression of the disease. This review focuses on where we are in our understanding of the disease, where we need to go to
understand the molecular triggers that set the process in motion, and what emergent therapeutic approaches show promise for
ameliorating disease progression in the clinic. |
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Keywords: | |
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