Basic Science and Pathogenesis.

Background: Frontotemporal dementia (FTD) presents with a change in personality, behaviour and language and is the second most common cause of young-onset dementia after Alzheimer's disease. Loss of function mutations in GRN, encoding progranulin (PGRN), causes FTD in the heterozygous state, accounting for 5-10% of all FTD cases. PGRN is essential for normal lysosomal function and neuronal survival.

Mutations in FUS lead to synaptic dysregulation in ALS-iPSC derived neurons.

Amyotrophic lateral sclerosis (ALS) is a fatal, adult-onset neurodegenerative disorder characterized by progressive muscular weakness due to the selective loss of motor neurons. Mutations in the gene Fused in Sarcoma (FUS) were identified as one cause of ALS. Here, we report that mutations in FUS lead to upregulation of synaptic proteins, increasing synaptic activity and abnormal release of vesicles at the synaptic cleft.

Targeting DNA Methylation in the Adult Brain through Diet.

Metabolism and nutrition have a significant role in epigenetic modifications such as DNA methylation, which can influence gene expression. Recently, it has been suggested that bioactive nutrients and gut microbiota can alter DNA methylation in the central nervous system (CNS) through the gut-brain axis, playing a crucial role in modulating CNS functions and, finally, behavior. Here, we will focus on the effect of metabolic signals in shaping brain DNA methylation during adulthood.

Elucidating the Role of Cerebellar Synaptic Dysfunction in C9orf72-ALS/FTD - a Systematic Review and Meta-Analysis.

A hexanucleotide repeat expansion in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) with synaptic dysfunction identified as an early pathological hallmark. Although TDP-43 pathology and overt neurodegeneration are largely absent from the cerebellum, the pathological hallmarks of RNA foci and dipeptide repeat protein (DPR) inclusions are most abundant. Here, we present a systematic literature search in the databases of PubMed, Scopus, Embase, Web of Science and Science Direct up until March 5, 2021, which yielded 19,515 publications.

Improving Age-Related Cognitive Decline through Dietary Interventions Targeting Mitochondrial Dysfunction.

Aging is inevitable and it is one of the major contributors to cognitive decline. However, the mechanisms underlying age-related cognitive decline are still the object of extensive research. At the biological level, it is unknown how the aging brain is subjected to progressive oxidative stress and neuroinflammation which determine, among others, mitochondrial dysfunction.

The Relationship between Choline Bioavailability from Diet, Intestinal Microbiota Composition, and Its Modulation of Human Diseases.

Choline is a water-soluble nutrient essential for human life. Gut microbial metabolism of choline results in the production of trimethylamine (TMA), which, upon absorption by the host is converted into trimethylamine-N-oxide (TMAO) in the liver. A high accumulation of both components is related to cardiovascular disease, inflammatory bowel disease, non-alcoholic fatty liver disease, and chronic kidney disease.