Research Topic

Multifaceted Genes in Amyotrophic Lateral Sclerosis-Frontotemporal Dementia

About this Research Topic

Amyotrophic Lateral Sclerosis-Frontotemporal Dementia (ALS-FTD) is a heterogeneous, multi-factorial and multi-systemic disease spectrum for which there are no effective drug treatments to date. Since the identification of SOD1 in 1993, the field of ALS-FTD genetics has greatly expanded. The advent of ...

Amyotrophic Lateral Sclerosis-Frontotemporal Dementia (ALS-FTD) is a heterogeneous, multi-factorial and multi-systemic disease spectrum for which there are no effective drug treatments to date. Since the identification of SOD1 in 1993, the field of ALS-FTD genetics has greatly expanded. The advent of high-throughput next generation sequencing technologies has enabled a system-wide unbiased approach to simultaneously identify genetic variation across the genome, in both disease-causing and disease-modifying genes, improving our understanding of the diverse pathogenic basis of ALS-FTD. Over 30 genetic loci have been reproducibly linked or associated with ALS-FTD and new genes are constantly being identified. It is now recognized that ALS and FTD constitute a disease spectrum or syndrome rather than single disorders. This scenario exemplifies the emerging observation of phenotypic pleiotropy, where mutations in the same gene give rise to diverse phenotypes, further increasing the complexity of phenotype-genotype correlation.

In 2011, the discovery that the C9orf72 GGGGCC repeat expansion is the main cause of ALS and FTD definitively consolidated the hypothesis that the two diseases belong to the same clinicopathological spectrum. Repeat expansions have emerged in recent years as major contributors to motor neuron degeneration. Intermediate-length CAG repeat expansions of both ATXN1 and ATXN2 have also been associated with an increased risk of developing ALS.

Mutations in the genes optineurin (OPTN), valosin containing protein (VCP), sequestosome 1 (SQSTM1), and matrin 3 (MATR3) offered insight into the connection of ALS-FTD with seemingly unrelated clinical disorders such as Paget's disease and myopathy.

Recently, kinesin family member 5A (KIF5A), a gene previously linked to two rare neurodegenerative disorders, hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth Type 2 (CMT2), has been definitively linked to ALS.

Taken together, these and other genes have highlighted the complex genetic architecture of ALS-FTD, with many genes in seemingly unrelated physiologic pathways producing a similar phenotype.

In this Research Topic, we aim to bring together knowledge on current research in ALS-FTD, providing an updated overview on genetic/genomic and clinical studies that aim to shed light on overlapping mechanisms of disease pathophysiology that may serve to unite disparate mutations under a common umbrella searching for disease-modifying therapies.


Keywords: ALS-FTD, genes, genomics, pathways, therapies


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30 September 2019 Manuscript

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Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

30 September 2019 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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