This Research Topic is part of the article collection series:
Molecular mechanisms and innovative therapeutic strategies for frontotemporal lobar degeneration.
Frontotemporal lobar degeneration (FTLD) is one of the most common causes of early-onset dementia. FTLD onset is characterized by progressive changes in behavior, personality, and language; as the disease progresses cognitive symptoms appear. The cognitive and behavioral impairments associated with FTLD interfere with successful engagement in daily life, such as parenting, working, and interpersonal relationships. FTLD is a clinically, pathologically, and genetically heterogeneous disorder. Histopathological heterogeneity includes intraneuronal inclusions, mostly positive for tau or ubiquitin, with frequent cases of TDP-43 positivity, and more rarely FUS reactivity. About 30% of FTLD patients are familial with an autosomal dominant pattern of transmission. Mutations in a number of genes are associated with FTLD, most commonly in MAPT or GRN, and C90RF72 genes, and more rarely in VCP, TARDBP or FUS. A pathological classification of FTLD was developed according to the presence of protein aggregates, namely FTLD-Tau, FTLD-TDP43, FTLD-FUS, FTLD-UBS. There is some degree of correlation between the clinical type and pathological findings and this correlation is important for effective and selective intervention. Moreover, specific biomarkers coupled to the genetic profile aimed to monitor disease onset and progression and/or therapy efficacy are to be searched, also considering innovative approaches. There are currently only very limited medications for the management of the cognitive-behavioral symptoms, but non-pharmacological interventions may offer significant benefits to the quality of life of the diagnosed individual (neurorehabilitation, community-based services to help successful re-engagement in life activities and promote improved quality of life).
At a molecular level, FTLD couples neurodegeneration and protein aggregation, and the basis of the pathogenic process is to be elucidated, also proposing a pivotal change of the point of view of the underlining degenerative pathways (for instance, by searching for soluble but toxic forms of the aggregation-prone proteins, or considering the role of microbiota(s) or the brain glymphatic system).
The therapeutic challenge implies many innovative approaches to be considered, for instance, novel nanotechnology and biomaterial-based strategies to deliver drugs or therapeutic proteins to the brain, also in vivo, cell-based therapies (including stem cells) and DNA/RNA in vivo delivery and the development of technological solutions for in vitro disease modeling (for instance, organ-on-a-chip).
This Research Topic aims at updating the state-of-the-art molecular, genetic, and therapeutic aspects of FTLD, by collecting contributions with a focus on novel pathogenic hypotheses, risk factors, multidisciplinary therapeutic approaches (both pharmacological or not), as well as disease models.
