Opposite effects of two estrogen receptors on tau phosphorylation through disparate effects on the miR-218/PTPA pathway.

The two estrogen receptors (ERs), ERα and ERβ, mediate the diverse biological functions of estradiol. Opposite effects of ERα and ERβ have been found in estrogen-induced cancer cell proliferation and differentiation as well as in memory-related tasks. However, whether these opposite effects are implicated in the pathogenesis of Alzheimer's disease (AD) remains unclear.

SUMOylation at K340 inhibits tau degradation through deregulating its phosphorylation and ubiquitination.

Intracellular accumulation of the abnormally modified tau is hallmark pathology of Alzheimer's disease (AD), but the mechanism leading to tau aggregation is not fully characterized. Here, we studied the effects of tau SUMOylation on its phosphorylation, ubiquitination, and degradation. We show that tau SUMOylation induces tau hyperphosphorylation at multiple AD-associated sites, whereas site-specific mutagenesis of tau at K340R (the SUMOylation site) or simultaneous inhibition of tau SUMOylation by ginkgolic acid abolishes the effect of small ubiquitin-like modifier protein 1 (SUMO-1).

Inhibition of glycogen synthase kinase-3 reverses tau hyperphosphorylation induced by Pin1 down-regulation.

One of the neuropathological hallmarks of Alzheimer's disease (AD) is the occurrence of neurofibrillary tangles (NFTs) that are composed of abnormally hyperphosphorylated microtubule-associated protein tau. Abnormal tau hyperphosphorylation is mainly induced due to the imbalance between protein kinases and phosphatases. In the tanglerich subregions of the hippocampus and parietal cortex in the brain of AD patients, the levels of the phosphorylationdependent protein peptidyl-prolyl cis-trans isomerase (Pin1) were found to be low.

Melatonin attenuates scopolamine-induced memory/synaptic disorder by rescuing EPACs/miR-124/Egr1 pathway.

Alzheimer's disease (AD) is the most prevalent type of dementia in elderly people. There are decreased melatonin levels in the serum of AD patients, and melatonin supplements are able to reverse AD pathology and memory deficits in many animal experiments and clinical trials. However, the underlying mechanism regarding how melatonin rescues the AD-like memory/synaptic disorder remains unknown.

Neuroglobin attenuates Alzheimer-like tau hyperphosphorylation by activating Akt signaling.

Neuroglobin (Ngb) is a recently identified member of hemoglobin family, distributed mainly in central and peripheral nervous systems. Recent studies suggest that Ngb can protect neural cells from β-amyloid-induced toxicity in Alzheimer disease (AD). Hyperphosphorylation of tau is another characterized pathological hallmark in the AD brains; however, it is not reported whether Ngb also affects tau phosphorylation.