Novel Insights into Amyotrophic Lateral Sclerosis (ALS)

Dear Colleagues,

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease involving the selective loss of upper and lower motor neurons. The morphological and neurobiological characteristics of motor neurons—including their large size, extensive axonal length, hypermetabolism, and electrophysiological properties—have been postulated as the basis for their disproportionate sensitivity. Whether the theoretical origin(s) of ALS specifically arise in motor neurons or if their intrinsic characteristics mandate lower neurodegenerative thresholds to neurotoxic insults remains unresolved. Furthermore, cellular pathology and disease mechanisms involving microglia, astrocytes, and other non-neuronal cell types are incompletely understood. Since current diagnostic criteria, biomarker repertoires, and outcome measures used in ALS clinical trials are defined by motor neuron involvement, further inquiry into the intrinsic and extrinsic factors that influence motor neuron survival is critical.

A recent surge of research focused on the TAR DNA binding protein 43 (TDP-43) has established a broad consensus that the nuclear exclusion and cytoplasmic accumulation of the protein represent a unifying disease process, rather than merely a neuropathological hallmark of ALS. Despite the efforts of TDP-43 reductionists, the cellular pathology and disease mechanisms involving TDP-43 have revealed an even more confounding pathophysiological landscape.

This Special Issue aims to increase fundamental understanding of the clinical syndrome by soliciting original research and review articles exploring the nexus of molecular and cellular pathogenesis in ALS. Authors are encouraged to share emerging research developments with the scientific community to better clarify the cascading homeostatic collapse of motor neurons emanating from both intrinsic and extrinsic sources. Research may address various aspects of disease involving genomic, transcriptomic, and proteomic deterioration, as well as conditions in which cells fail to successfully respond to nocuous molecular decay. Research may be devoted to cytoskeletal and synaptic compositions and dynamics under pathological conditions. The involvement of complex molecular machinery, membrane-bound organelles, and the biophysical dynamics of membrane-less organelles is also relevant. Authors are further welcome to report on the role of inflammation, astrocytic support, intercellular signaling, and other non-cell-autonomous influences on neuronal survival. Bearing in mind that age is the primary risk factor in ALS and that cellular pathology may accumulate for many years prior to overt phenotypic manifestations, research devoted to sub-threshold and disease-initiating insults is of particular interest.

Dr. Zane Zeier
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.