Since microtubule - Tau organization and dynamics is central in axonal microtubule cytoskeleton and transport, tightly related to aging processes and Alzheimer's disease, our current study provides a compelling molecular explanation to the <i>in vivo</i> activity of SKIP, placing SKIP motif as a central focus for MT-based neuroprotection in tauopathies with axonal transport implications.
These data identify an important role of microglia and NLRP3 inflammasome activation in the pathogenesis of tauopathies and support the amyloid-cascade hypothesis in Alzheimer's disease, demonstrating that neurofibrillary tangles develop downstream of amyloid-beta-induced microglial activation.
Since microtubule - Tau organization and dynamics is central in axonal microtubule cytoskeleton and transport, tightly related to aging processes and Alzheimer's disease, our current study provides a compelling molecular explanation to the <i>in vivo</i> activity of SKIP, placing SKIP motif as a central focus for MT-based neuroprotection in tauopathies with axonal transport implications.
Histopathologically, the alkaloidal fraction-treated 3xTg-AD mice exhibited a significant reduction in tauopathy and astrogliosis, as well as a significant decrease in the proinflammatory marker COX-2 and an increase in pAkt.
We identified three microRNAs (miR-150-5p, miR-155-5p, miR-375-3p) that were down-regulated in 16-week-old hTau mice, which do not yet exhibit a behavioral phenotype and therefore represent pre-symptomatic tauopathy.
Using transgenic or viral approaches, we characterized in mice the effects of TYROBP deficiency on the phenotypic and pathological evolution of tauopathy.
We conducted systematic and quantitative immunohistochemistry for glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (Iba1), amyloid beta, and highly phosphorylated tau (tauopathy).
These results suggest that USP13 inhibition may be a therapeutic strategy to reduce accumulation of plaques and toxic p-tau in AD and human tauopathies.
These data show that metformin may reduce tauopathy and improve cognitive impairment in db/db mice by modulating autophagy through the AMPK dependent pathway.
In a word, our results uncover the aggregation and misfolding mechanism of PHF6 from the atomic level, which can provide useful theoretical guidance for rational design of effective therapeutic drugs against tauopathies.
Histopathologically, the alkaloidal fraction-treated 3xTg-AD mice exhibited a significant reduction in tauopathy and astrogliosis, as well as a significant decrease in the proinflammatory marker COX-2 and an increase in pAkt.
However, when the concentration was high (10.24 μM), amylin lost the effects against the Aβ-induced cellular AD pathology and, together with Aβ, worsened tauopathy in neurons.
These data show that metformin may reduce tauopathy and improve cognitive impairment in db/db mice by modulating autophagy through the AMPK dependent pathway.
Here, using a transgenic mouse model and primary cell cultures along with quantitative PCR, immunoblotting, and immunohistochemistry, we tested whether the UPR is induced in <i>in vivo</i> and <i>in vitro</i> murine models of tauopathy that are based on expression of mutant tau<sup>P301L</sup> We found no evidence for the UPR in the rTg4510 mouse model, in which mutant tau is transgenically expressed under the control of tetracycline-controlled transactivator protein.
We conducted systematic and quantitative immunohistochemistry for glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor molecule 1 (Iba1), amyloid beta, and highly phosphorylated tau (tauopathy).
These data show that metformin may reduce tauopathy and improve cognitive impairment in db/db mice by modulating autophagy through the AMPK dependent pathway.
Tau deposits were often associated with slight myelin disruption and the presence of small PLP1-immunoreactive globules and dots in the ipsilateral corpus callosum 6 months after inoculation of sarkosyl-insoluble fractions from every tauopathy.