TRIM37 is a primate-specific E3 ligase for Huntingtin and accounts for the striatal degeneration in Huntington's disease.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterized by preferential neuronal loss in the striatum. The mechanism underlying striatal selective neurodegeneration remains unclear, making it difficult to develop effective treatments for HD. In the brains of nonhuman primates, we examined the expression of Huntingtin (), the gene responsible for HD.

Surface-modified silicalite-1-filled PDMS membranes for pervaporation dehydration of trichloroethylene.

In this study, the impact of silane coupling agents, namely 3-aminopropyltrimethoxysilane (APTMS), trimethylchlorosilane (TMCS), and 1,1,3,3-tetramethyldisilazane (TMDS), on the hydrophobicity of silicalite-1 zeolite was investigated to enhance the pervaporation separation performance of mixed matrix membranes (MMMs) for trichloroethylene (TCE). The hydrophobicity of TMCS@silicalite-1 and TMDS@silicalite-1 particles exhibited significant improvement, as evidenced by the increase in water contact angle from 96.1° to 101.

Improving the Pervaporation Performance of PDMS Membranes for Trichloroethylene by Incorporating Silane-Modified ZSM-5 Zeolite.

The hydrophobic nature of inorganic zeolite particles plays a crucial role in the efficacy of mixed matrix membranes (MMMs) for the separation of trichloroethylene (TCE) through pervaporation. This study presents a novel approach to further augment the hydrophobicity of ZSM-5. The ZSM-5 zeolite molecular sieve was subjected to modification using three different silane coupling agents, namely, n-octyltriethoxysilane (OTES), γ-methacryloxypropyltrimethoxysilane (KH-570), and γ-aminopropyltriethoxysilane (KH-550).

A Specific Mini-Intrabody Mediates Lysosome Degradation of Mutant Huntingtin.

Accumulation of misfolded proteins leads to many neurodegenerative diseases that can be treated by lowering or removing mutant proteins. Huntington's disease (HD) is characterized by the intracellular accumulation of mutant huntingtin (mHTT) that can be soluble and aggregated in the central nervous system and causes neuronal damage and death. Here, an intracellular antibody (intrabody) fragment is generated that can specifically bind mHTT and link to the lysosome for degradation.

Generation of inactivated IL2RG and RAG1 monkeys with severe combined immunodeficiency using base editing.

Severe combined immunodeficiency (SCID) encompasses a range of inherited disorders that lead to a profound deterioration of the immune system. Among the pivotal genes associated with SCID, RAG1 and IL2RG play crucial roles. IL2RG is essential for the development, differentiation, and functioning of T, B, and NK cells, while RAG1 critically contributes to adaptive immunity by facilitating V(D)J recombination during the maturation of lymphocytes.

Physical exercise modulates the microglial complement pathway in mice to relieve cortical circuitry deficits induced by mutant human TDP-43.

The aggregation of TAR DNA binding protein 43 kDa (TDP-43) is related to different neurodegenerative diseases, which leads to microglial activation and neuronal loss. The molecular mechanism driving neuronal death by reactive microglia, however, has not been completely resolved. In this study, we generated a mouse model by overexpressing mutant human TDP-43 (M337V) in the primary motor cortex, leading to prominent motor-learning deficits.

Cas9-mediated replacement of expanded CAG repeats in a pig model of Huntington's disease.

The monogenic nature of Huntington's disease (HD) and other neurodegenerative diseases caused by the expansion of glutamine-encoding CAG repeats makes them particularly amenable to gene therapy. Here we show the feasibility of replacing expanded CAG repeats in the mutant HTT allele with a normal CAG repeat in genetically engineered pigs mimicking the selective neurodegeneration seen in patients with HD. A single intracranial or intravenous injection of adeno-associated virus encoding for Cas9, a single-guide RNA targeting the HTT gene, and donor DNA containing the normal CAG repeat led to the depletion of mutant HTT in the animals and to substantial reductions in the dysregulated expression and neurotoxicity of mutant HTT and in neurological symptoms.

Intravenous AAV9 administration results in safe and widespread distribution of transgene in the brain of mini-pig.

Animal models are important for understanding the pathogenesis of human diseases and for developing and testing new drugs. Pigs have been widely used in the research on the cardiovascular, skin barrier, gastrointestinal, and central nervous systems as well as organ transplantation. Recently, pigs also become an attractive large animal model for the study of neurodegenerative diseases because their brains are very similar to human brains in terms of mass, gully pattern, vascularization, and the proportions of the gray and white matters.

TBN improves motor function and prolongs survival in a TDP-43M337V mouse model of ALS.

Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are serious neurodegenerative diseases. Although their pathogenesis is unclear, the abnormal accumulation of TAR DNA-binding protein of 43 kDa (TDP-43) is a pathological feature that exists in almost all patients. Thus far, there is no drug that can cure ALS/FTLD.

Differential development and electrophysiological activity in cultured cortical neurons from the mouse and cynomolgus monkey.

In vitro cultures of primary cortical neurons are widely used to investigate neuronal function. However, it has yet to be fully investigated whether there are significant differences in development and function between cultured rodent and primate cortical neurons, and whether these differences influence the utilization of cultured cortical neurons to model pathological conditions. Using in vitro culture techniques combined with immunofluorescence and electrophysiological methods, our study found that the development and maturation of primary cerebral cortical neurons from cynomolgus monkeys were slower than those from mice.