Progranulin and frontotemporal lobar degeneration.
Frontotemporal lobar degeneration is the term used to describe the non-Alzheimer clinical syndromes of frontotemporal dementia, semantic dementia and progressive non-fluent aphasia, regardless of the underlying neuropathological features. Considerable progress has been made in recent years in our understanding of the aetiology of this disorder, notably the identification of mutations in tau and progranulin genes, both on chromosome 17q21. Mutations in tau appear to affect the ability of tau to bind microtubules and/or increase this protein's ability to form fibrils. In contrast, progranulin mutations cause haploinsufficiency leading to TDP-43 accumulation. These genes collectively account for 10-20% of FTLD. However, it is clear that much remains to be discovered before our knowledge of this heterogeneous condition is complete.
Pickering-Brown
Stuart M
SM
Division of Regenerative Medicine, Stopford Building, University of Manchester, Oxford Road, Manchester, M13 9PT, UK. SPB@Manchester.ac.uk
D004268:DNA-Binding Proteins / Q000378:metabolism; D003704:Dementia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D000077153:Progranulins; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
D004268:DNA-Binding Proteins; C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; C054369:MAPT protein, human; D000077153:Progranulins; D016875:tau Proteins