期刊
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
卷 42, 期 3, 页码 220-241出版社
WILEY
DOI: 10.1111/nan.12242
关键词
autophagy; mitochondria; NBIA; neurodegeneration; Tau; -synuclein
资金
- Wellcome Trust
- Medical Research Council
- Dystonia Coalition
- Bachmann-Strauss Dystonia and Parkinson Foundation
- Eli Lilly
- National Institute for Health Research (NIHR) Biomedical Research Unit in Dementia based at University College London Hospitals (UCLH), University College London (UCL)
- Medical Research Council [G1001253, MR/J004758/1, G0802760, G108/638] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0515-10082] Funding Source: researchfish
- MRC [G108/638, G1001253, MR/J004758/1, G0802760] Funding Source: UKRI
Neurodegeneration with brain iron accumulation (NBIA) is a group of disorders characterized by dystonia, parkinsonism and spasticity. Iron accumulates in the basal ganglia and may be accompanied by Lewy bodies, axonal swellings and hyperphosphorylated tau depending on NBIA subtype. Mutations in 10 genes have been associated with NBIA that include Ceruloplasmin (Cp) and ferritin light chain (FTL), both directly involved in iron homeostasis, as well as Pantothenate Kinase 2 (PANK2), Phospholipase A2 group 6 (PLA2G6), Fatty acid hydroxylase 2 (FA2H), Coenzyme A synthase (COASY), C19orf12, WDR45 and DCAF17 (C2orf37). These genes are involved in seemingly unrelated cellular pathways, such as lipid metabolism, Coenzyme A synthesis and autophagy. A greater understanding of the cellular pathways that link these genes and the disease mechanisms leading to iron dyshomeostasis is needed. Additionally, the major overlap seen between NBIA and more common neurodegenerative diseases may highlight conserved disease processes. In this review, we will discuss clinical and pathological findings for each NBIA-related gene, discuss proposed disease mechanisms such as mitochondrial health, oxidative damage, autophagy/mitophagy and iron homeostasis, and speculate the potential overlap between NBIA subtypes.
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