Beneficial effects of miR-132/212 deficiency in the zQ175 mouse model of Huntington's disease.

Huntington's disease (HD) is a rare genetic neurodegenerative disorder caused by an expansion of CAG repeats in the Huntingtin (HTT) gene. One hypothesis suggests that the mutant HTT gene contributes to HD neuropathology through transcriptional dysregulation involving microRNAs (miRNAs). In particular, the miR-132/212 cluster is strongly diminished in the HD brain.

Higher Angiotensin I Converting Enzyme 2 (ACE2) levels in the brain of individuals with Alzheimer's disease.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a major cause of death in the elderly. Cognitive decline due to Alzheimer's disease (AD) is frequent in the geriatric population disproportionately affected by the COVID-19 pandemic. Interestingly, central nervous system (CNS) manifestations have been reported in SARS-CoV-2-infected patients.

Marker-free co-selection for successive rounds of prime editing in human cells.

Prime editing enables the introduction of precise point mutations, small insertions, or short deletions without requiring donor DNA templates. However, efficiency remains a key challenge in a broad range of human cell types. In this work, we design a robust co-selection strategy through coediting of the ubiquitous and essential sodium/potassium pump (Na/K ATPase).

Widespread alterations in microRNA biogenesis in human Huntington's disease putamen.

Altered microRNA (miRNA) expression is a common feature of Huntington's disease (HD) and could participate in disease onset and progression. However, little is known about the underlying causes of miRNA disruption in HD. We and others have previously shown that mutant Huntingtin binds to Ago2, a central component of miRNA biogenesis, and disrupts mature miRNA levels.

MicroRNA-138 Overexpression Alters Aβ42 Levels and Behavior in Wildtype Mice.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by changes in cognitive and behavioral functions. With the exception or rare mutations in PSEN and APP genes causing early-onset autosomal dominant AD (EOADAD), little is known about the genetic factors that underlie the vast majority (>95%) of early onset AD (EOAD) cases. We have previously identified copy number variations (CNVs) in microRNA genes in patients with EOAD, including a duplication of the MIR-138-2 gene.

Advances and Challenges in Understanding MicroRNA Function in Tauopathies: A Case Study of miR-132/212.

In the past decade, several groups have reported that microRNAs (miRNAs) can participate in the regulation of tau protein at different levels, including its expression, alternative splicing, phosphorylation, and aggregation. These observations are significant, since the abnormal regulation and deposition of tau is associated with nearly 30 neurodegenerative disorders. Interestingly, miRNA profiles go awry in tauopathies such as Alzheimer's disease, progressive supranuclear palsy, and frontotemporal dementia.