About this Research Topic
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two intrinsically linked neurodegenerative disorders that overlap at genetic, neuropathological, and clinical levels. It has been increasingly recognized that ALS and FTD share common molecular mechanisms and may in fact represent two ends of one disease spectrum named `ALS-FTD spectrum'. The identification of this striking overlap between FTD and ALS has not only widened the clinical scope of disease heterogeneity but also highlighted a novel understanding of molecular pathology. The past decade has witnessed a dramatic increase in the discovery of novel pathogenic mechanisms, novel mutations, and therapeutic interventions associated with ALS-FTD spectrum. These discoveries have challenged our concepts of disease progression and promoted the translational application of basic research findings.
A multitude of genes encompassing diverse variants have been associated with ALS-FTD spectrum, and at least 11 susceptibility genes are in common. Discoveries of these genes have shed light on understanding major molecular pathways involved in neurodegeneration, including DNA/RNA metabolism, protein homeostasis, mitochondrial stress, microtubule dynamics, etc. However, the exact molecular network still needs to be fully elucidated. Notably, a substantial number of patients suffer from the sporadic form without a clear underlying genetic disposition. Interestingly, neuroinflammation characterized by innate immune responses of tissue-resident glial cells is uniformly present as end-stage pathology in ALS-FTD spectrum patients. Changes in circulating immune cell populations and cytokines that represent systemic inflammation are found in those patients. While it remains debatable whether inflammation is simply a consequence of disease or plays a causal role, there is no doubt that inflammation plays an important role in disease progression. Overall, interactions between genetic makeups, molecular mechanisms, and environmental factors form a comprehensive regulatory network in pathogenesis and influence the disease progression.
In addition, recent findings in new biomarkers and epidemiologic features in ALS-FTD spectrum have not only enhanced the precision of clinical diagnosis and predications, but also complemented our understanding of the pathological mechanisms.
In summary, ALS-FTD spectrum is a complicated disease spectrum with a flourishing research finding in molecular mechanisms during the past decades. A disease-specific collection of the comprehensive discoveries underlying pathogenic mechanisms in ALS-FTD spectrum will be a great interest to a broad audience.
This research topic aims to generate a multidimensional discussion on the current concept and translational study in the ALS-FTD spectrum, with a special focus on molecular mechanisms in pathogenesis. We are particularly interested in research related to endogenous and exogenous factors contributing to disease progression, molecular networks interconnecting all the genetic players, as well as altered pathological aspects with a focus on neuroinflammation profiles. Findings from this research could potentially help identifying novel biomarkers for preclinical diagnosis and clinical evaluation of disease progression, which could eventually contribute to the development of effective, personalized therapeutic strategies.
In this context, we welcome original articles and reviews based on the following sub-themes:
• Clinical investigation on the epidemiology, genetics, early diagnosis, and treatment of ALS-FTD spectrum.
• Biomarkers of ALS/FTD spectrum disorders.
• Insights into the role of neuroinflammation in the pathogenesis of ALS-FTD spectrum.
• Novel molecular mechanisms underlying neurodegeneration in ALS-FTD spectrum.
• Research progress on sporadic ALS, FTD and other related types of dementia are also welcomed.
We would like to acknowledge that Dr. Dingding Shen, Shanghai Ruijin Hospital, Shanghai, China, has acted as a coordinator and has contributed to the preparation of the proposal for this Research Topic.
A multitude of genes encompassing diverse variants have been associated with ALS-FTD spectrum, and at least 11 susceptibility genes are in common. Discoveries of these genes have shed light on understanding major molecular pathways involved in neurodegeneration, including DNA/RNA metabolism, protein homeostasis, mitochondrial stress, microtubule dynamics, etc. However, the exact molecular network still needs to be fully elucidated. Notably, a substantial number of patients suffer from the sporadic form without a clear underlying genetic disposition. Interestingly, neuroinflammation characterized by innate immune responses of tissue-resident glial cells is uniformly present as end-stage pathology in ALS-FTD spectrum patients. Changes in circulating immune cell populations and cytokines that represent systemic inflammation are found in those patients. While it remains debatable whether inflammation is simply a consequence of disease or plays a causal role, there is no doubt that inflammation plays an important role in disease progression. Overall, interactions between genetic makeups, molecular mechanisms, and environmental factors form a comprehensive regulatory network in pathogenesis and influence the disease progression.
In addition, recent findings in new biomarkers and epidemiologic features in ALS-FTD spectrum have not only enhanced the precision of clinical diagnosis and predications, but also complemented our understanding of the pathological mechanisms.
In summary, ALS-FTD spectrum is a complicated disease spectrum with a flourishing research finding in molecular mechanisms during the past decades. A disease-specific collection of the comprehensive discoveries underlying pathogenic mechanisms in ALS-FTD spectrum will be a great interest to a broad audience.
This research topic aims to generate a multidimensional discussion on the current concept and translational study in the ALS-FTD spectrum, with a special focus on molecular mechanisms in pathogenesis. We are particularly interested in research related to endogenous and exogenous factors contributing to disease progression, molecular networks interconnecting all the genetic players, as well as altered pathological aspects with a focus on neuroinflammation profiles. Findings from this research could potentially help identifying novel biomarkers for preclinical diagnosis and clinical evaluation of disease progression, which could eventually contribute to the development of effective, personalized therapeutic strategies.
In this context, we welcome original articles and reviews based on the following sub-themes:
• Clinical investigation on the epidemiology, genetics, early diagnosis, and treatment of ALS-FTD spectrum.
• Biomarkers of ALS/FTD spectrum disorders.
• Insights into the role of neuroinflammation in the pathogenesis of ALS-FTD spectrum.
• Novel molecular mechanisms underlying neurodegeneration in ALS-FTD spectrum.
• Research progress on sporadic ALS, FTD and other related types of dementia are also welcomed.
We would like to acknowledge that Dr. Dingding Shen, Shanghai Ruijin Hospital, Shanghai, China, has acted as a coordinator and has contributed to the preparation of the proposal for this Research Topic.
Keywords: ALS, dementia, genetics, pathogenesis, neuroinflammation, neurodegeneration
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