In vivo cyclic overexpression of Yamanaka factors restricted to neurons reverses age-associated phenotypes and enhances memory performance.

In recent years, there has been success in partially reprogramming peripheral organ cells using cyclic Yamanaka transcription factor (YF) expression, resulting in the reversal of age-related pathologies. In the case of the brain, the effects of partial reprogramming are scarcely known, and only some of its effects have been observed through the widespread expression of YF. This study is the first to exclusively partially reprogram a specific subpopulation of neurons in the cerebral cortex of aged mice.

Pharmacological inhibition of mTORC1 reduces neural death and damage volume after MCAO by modulating microglial reactivity.

Ischemic stroke is a sudden and acute disease characterized by neuronal death, increment of reactive gliosis (reactive microglia and astrocytes), and a severe inflammatory process. Neuroinflammation is an early event after cerebral ischemia, with microglia playing a leading role. Reactive microglia involve functional and morphological changes that drive a wide variety of phenotypes.

Intron retention as a productive mechanism in human MAPT: RNA species generated by retention of intron 3.

Background: Tau is a microtubule-binding protein encoded by the MAPT gene. Tau is essential for several physiological functions and associated with pathological processes, including Alzheimer's disease (AD). Six tau isoforms are typically described in the central nervous system, but current research paints a more diverse landscape and a more nuanced balance between isoforms.

Lamivudine (3TC), a Nucleoside Reverse Transcriptase Inhibitor, Prevents the Neuropathological Alterations Present in Mutant Tau Transgenic Mice.

The dysregulation of transposable elements contributes to neurodegenerative disorders. Previous studies have reported an increase in retrotransposon transcription in models as well as in human tauopathies. In this context, we tested the possible protective effects of a reverse transcriptase inhibitor, namely lamivudine (also known as 3TC), in P301S mice, an animal model of Alzheimer's disease based on FTDP-17-tau overexpression.

Mouse and Human Tau Expression in Different Brain Areas.

Background: An increase in tau protein is believed to be necessary for tau aggregation. However, whether this is due to increased expression of the endogenous tau promoter or protein accumulation due to proteostasis failure remains uncertain.

Objective: To analyze the expression of GFP protein under endogenous tau promoter across different ages and within different brain areas.

Neuronal nuclear tau and neurodegeneration.

Tau is a well-known microtubule-associated protein related to its cytoplasmic localization in a neuronal cell. However, tau has been located at the cell nucleus where it could be a nucleic acid-associated protein by its preferential binding to DNA sequences present in the nucleolus and pericentromeric heterochromatin. This less well-known localization of tau could not be trivial, since during aging, an increase in the amount of nuclear tau takes place and it may be related to the described role of tau in the activation of transposons and further aging acceleration.

p38 activation occurs mainly in microglia in the P301S Tauopathy mouse model.

Tauopathies are a group of neurodegenerative diseases characterized by the accumulation of hyperphosphorylated tau protein in the brain. Many of these pathologies also present an inflammatory component determined by the activation of microglia, the resident immune cells of the brain. p38 MAPK is one of the molecular pathways involved in neuroinflammation.

Microtubule-associated protein tau in murine kidney: role in podocyte architecture.

Tau is a cytoskeletal protein that is expressed mainly in neurons and is involved in several cellular processes, such as microtubule stabilization, axonal maintenance, and transport. Altered tau metabolism is related to different tauopathies being the most important Alzheimer's disease where aberrant hyperphosphorylated and aggregated tau is found in the central nervous system. Here, we have analyzed that function in kidney by using tau knockout mice generated by integrating GFP-encoding cDNA into exon 1 of MAPT (here referred to as Tau).

Focal cerebral ischemia induces changes in oligodendrocytic tau isoforms in the damaged area.

Ischemic stroke is a major cause of death and the first leading cause of long-term disability worldwide. The only therapeutic strategy available to date is reperfusion and not all the patients are suitable for this treatment. Blood flow blockage or reduction leads to considerable brain damage, affecting both gray and white matter.

Differences Between Human and Murine Tau at the N-terminal End.

Human tauopathies, such as Alzheimer's disease (AD), have been widely studied in transgenic mice overexpressing human tau in the brain. The longest brain isoforms of Tau in mice and humans show 89% amino acid identity; however, the expression of the isoforms of this protein in the adult brain of the two species differs. Tau 3R isoforms are not present in adult mice.

Generation and characterization of the human iPSC line CABi001-A from a patient with retinitis pigmentosa caused by a novel mutation in PRPF31 gene.

PRPF31 gene codes for a ubiquitously expressed splicing factor but mutations affect exclusively the retina, producing the progressive death of photoreceptor cells. We have identified a novel PRPF31 mutation in a patient with autosomal dominant retinitis pigmentosa. A blood sample was obtained and mononuclear cells were reprogrammed using the non-integrative Sendai virus to generate the cell line CABi001-A.