Back to Search
Start Over
Isoprenoids and tau pathology in sporadic Alzheimer's disease
- Source :
- Neurobiology of aging. 65
- Publication Year :
- 2017
-
Abstract
- The mevalonate pathway has been described to play a key role in Alzheimer's disease (AD) physiopathology. Farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) are nonsterol isoprenoids derived from mevalonate, which serve as precursors to numerous human metabolites. They facilitate protein prenylation; hFPP and hGGPP synthases act as gateway enzymes to the prenylation of the small guanosine triphosphate (GTP)ase proteins such as RhoA and cdc42 that have been shown to facilitate phospho-tau (p-Tau, i.e., protein tau phosphorylated) production in the brain. In this study, a significant positive correlation was observed between the synthases mRNA prevalence and disease status (FPPS, p0.001, n = 123; GGPPS, p0.001, n = 122). The levels of mRNA for hFPPS and hGGPPS were found to significantly correlate with the amount of p-Tau protein levels (p0.05, n = 34) and neurofibrillary tangle density (p 0.05, n = 39) in the frontal cortex. Interestingly, high levels of hFPPS and hGGPPS mRNA prevalence are associated with earlier age of onset in AD (p0.05, n = 58). Together, these results suggest that accumulation of p-Tau in the AD brain is related, at least in part, to increased levels of neuronal isoprenoids.
- Subjects :
- 0301 basic medicine
Male
Aging
RHOA
Geranylgeranyl pyrophosphate
Tau protein
Farnesyl pyrophosphate
Protein Prenylation
Mevalonic Acid
tau Proteins
Guanosine triphosphate
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Prenylation
Polyisoprenyl Phosphates
Alzheimer Disease
Cerebellum
Farnesyltranstransferase
Humans
cdc42 GTP-Binding Protein
Aged
Aged, 80 and over
biology
Terpenes
General Neuroscience
Geranyltranstransferase
Neurofibrillary Tangles
Frontal Lobe
030104 developmental biology
Biochemistry
chemistry
biology.protein
Protein prenylation
Female
Neurology (clinical)
Mevalonate pathway
Geriatrics and Gerontology
rhoA GTP-Binding Protein
Sesquiterpenes
030217 neurology & neurosurgery
Developmental Biology
Subjects
Details
- ISSN :
- 15581497
- Volume :
- 65
- Database :
- OpenAIRE
- Journal :
- Neurobiology of aging
- Accession number :
- edsair.doi.dedup.....46db65133f18ca26b4a188ed0b05229d