All of the neurodegenerative diseases discussed above had the common characteristic that changes in GSH content were observed in samples from Trilostane affected patients compared to controls, regardless of whether they were post mortem brain samples or blood samples from live human subjects.However, the difficulty with GSH as a specific biomarker is that differences in GSH content could be due to a variety of dietary and environmental factors, and changes in GSH levels have been implicated also in other diseases ranging from diabetes to cancer.Disruption in GSH homeostasis and modification of the enzymes that are dependent on GSH as a substrate have been linked to initiation and progression of the neurodegenerative diseases.Nutrients. Nutrients. Nutrients. PLoS One, e.Neuroreport. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license. In the tauopathies, pathological tau is in an elevated state of phosphorylation and is aberrantly Amorolfine hydrochloride cleaved.It also exhibits abnormal conformations and becomes aggregated, resulting in neurobrillary tau pathology.Recent evidence suggests that relatively early diseaseassociated changes in soluble tau proteins, including phosphorylation, are involved in the induction of neuronal death.Here, we summarize recent developments that suggest new therapeutic strategies to prevent or reduce the progression of pathology in the tauopathies.A list of tau phosphorylation sites identied in the tauopathies and in controls accompanies this review.Increasing age is the most signicant risk factor for dementia, with of the population being affected at years of age, increasing to more than from the age of. Currently, in excess of million people worldwide are suffering from dementia and thus therapies for AD are urgently needed.If no new treatments for AD become available, the number of affected individuals is predicted to reach million by. Existing treatments for AD do not effectively halt or slow disease progression, and this is due in part to a lack of knowledge of the mechanisms involved in disease pathogenesis.These various inclusions are comprised of insoluble, highly phosphorylated forms of tau and are likely to play a part in the neuronal loss evident in tauopathies. Recent evidence suggests that targeting tau phosphorylation through inhibition of protein kinases could represent a valid therapeutic approach to reduce tau aggregation and associated neuronal death. However, given the large number of phosphorylation sites and the many protein kinases implicated in tau phosphorylation, the potential therapeutic targets are numerous. In this review, we summarize current knowledge of tau phosphorylation in disease and consider how this could be targeted in AD and other tauopathies.The R:R tau ratios for both mRNA and protein are approximately equal in normal brain, but disturbances, usually increases, in these ratios occur in most of the neurodegenerative tauopathies.In the case of tau, exons, and are variably included in the mature transcript for the translation of six CNS isoforms.Amyloid: in the context of neurodegenerative disease, amyloid is misfolded protein that forms an extracellular aggregate with bpleated sheet structure.Neurodegeneration: the process of progressive loss of neurons in diseased brain.Neurofibrillary tangles: filaments of proteins deposited within neurons; a characteristic pathological feature of AD brain.