The specific tau isoforms, such as 3-repeat (3R) and 4-repeat (4R) isoforms, and the distinct conformational strains that misfolded tau can adopt are determinants of the molecular and clinical heterogeneity observed across tauopathies.
In a newly published study, researchers from the CSIR Institute of Genomics and Integrative Biology and collaborators further explored the potential of Cdk5 targeting as a therapeutic approach for type 2 diabetes and cognitive deterioration.
Scientists from the Machine Intelligence from Cortical Networks (MICRONS) consortium have published the microconnectome of a cubic millimeter of the mouse brain. This is the most complete map of this organ to date at nanometer resolution for a mammal. It not only contains the structure and connections of each and every cell in that volume of tissue, but is also linked to the neuronal activity of that portion of the CNS, linking anatomy and function in the same cells.
In Parkinson’s disease (PD), damaged mitochondria build up in the dopaminergic system of the substantia nigra, partly due to impaired mitochondrial autophagy (mitophagy) and autophagosome accumulation.
Nitrated α-synuclein is upregulated in the CSF of patients with Parkinson’s Disease (PD), Lewy body dementia (DLB), multiple system atrophy (MSA), and other synucleinopathies.
Researchers from Voyager Therapeutics Inc. presented preclinical activity data of VY-1706, a blood-brain barrier (BBB)-penetrant gene therapy comprising an adeno-associated virus serotype 9 capsid (AAV9-C9P39) vector encoding primary artificial microRNA (pri-amiRNA) consisting of short-interfering RNA (siRNA) targeting human microtubule-associated protein tau (MAPT) protein.
Metachromatic leukodystrophy (MLD) is an autosomal recessive lysosomal storage disease originating from biallelic pathogenic variants in the ARSA gene, mainly affecting young children.
Writing in Molecular Therapy Nucleic Acids, researchers hypothesized that using poly(A) tail mimetics to enhance mRNA expression from haploinsufficiency-associated genes could be a disease-modifying treatment strategy.
Researchers from Sanofi SA reported the preclinical characterization of SAR-446159 (ABL-301), a bispecific antibody construct comprising an antibody targeting α-synuclein fused to an engineered antibody fragment that targets IGF-1R and functions as a blood-brain barrier (BBB) shuttle, known as the Grabody-B platform.
BDNF is the brain’s most abundant neurotrophic factor, playing a key role in neuronal survival and synaptic plasticity through the activation of the transcription factor CREB, which is essential for driving beneficial effects in neurons. CREB is downregulated in Parkinson’s disease, Huntington’s disease, frontotemporal dementia, Alzheimer’s disease and other neurodegenerative conditions.