This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.

Neurodegenerative disorders encompass a broad range of sporadic and/or familial debilitating conditions characterized by the progressive dysfunction and loss of selective neuronal populations, determining different clinical phenotypes. Emerging research data indicate an interplay of genetic factors and epigenetic mechanisms underlying neurodegenerative processes, which lead to increased prevalence of neurodegenerative disorders. In concert with the constant increase in the aging population, neurodegenerative disorders currently represent a major challenge to public health worldwide. Despite recent advances in clinical and preclinical research, the pathogenesis of these disorders still remains poorly understood, without effective treatments being available to halt the neurodegenerative processes, but rather aiming at relieving symptoms. Therefore, a critical evaluation of current research data and in-depth understanding of the molecular mechanisms that lead to neurodegeneration are crucial in order to identify potential therapeutic targets that can pave the way to the development of novel and promising therapies. This Special Issue is focused on novel molecular data in the field of neurodegeneration that associate with the onset and progression of neurodegenerative diseases. We are particularly interested in original articles and reviews that provide new insights into the main molecular pathogenic mechanisms underlying neurodegenerative disorders, aiming to identify potential biomarkers and novel therapeutic strategies.

Neurodegenerative disorders encompass a broad range of sporadic and/or familial debilitating conditions characterized by the progressive dysfunction and loss of selective neuronal populations, determining different clinical phenotypes. Emerging research data indicate an interplay of genetic factors and epigenetic mechanisms underlying neurodegenerative processes, which lead to increased prevalence of neurodegenerative disorders. In concert with the constant increase in the aging population, neurodegenerative disorders currently represent a major challenge to public health worldwide. Despite recent advances in clinical and preclinical research, the pathogenesis of these disorders still remains poorly understood, without effective treatments being available to halt the neurodegenerative processes, but rather aiming at relieving symptoms. Therefore, a critical evaluation of current research data and in-depth understanding of the molecular mechanisms that lead to neurodegeneration are crucial in order to identify potential therapeutic targets that can pave the way to the development of novel and promising therapies. This Special Issue is focused on novel molecular data in the field of neurodegeneration that associate with the onset and progression of neurodegenerative diseases. We are particularly interested in original articles and reviews that provide new insights into the main molecular pathogenic mechanisms underlying neurodegenerative disorders, aiming to identify potential biomarkers and novel therapeutic strategies.

The complex etiology of neurodegenerative diseases is not fully understood, and the characterization of cellular pathways that are dysfunctional in these diseases is key for therapeutic development. Chemical and genetic perturbagens can probe cellular pathways to shed insight about both disease etiology and potential therapeutic targets. We analyzed the functional effects of chemical perturbagens in neurodegenerative disease models as evidenced by changes in transcriptomic, metabolomic, epigenomic, and proteomic data ("multi-omics" data). Our studies revealed novel modes of action for small molecule compounds that promote survival in a model of Huntington's Disease, a fatal neurodegenerative disorder. Integration of our multi-omics data using an interpretable network approach revealed that the autophagy and bioenergetics cellular pathways are affected by different sets of compounds that promote survival. Using staining and western blot assays, we validated the effect on autophagy for one set of compounds and found that the compounds activate this pathway. Using a cellular bioenergetics assay, we found that a second set of compounds shifts the bioenergetic flux from mitochondrial respiration to glycolysis, validating our network results. In a second study related to Huntington's Disease, we analyzed the effects of two peripheral huntingtin gene silencing techniques in mouse liver. We show that the transcriptional and metabolomic changes associated with both genetic silencing methods converge on similar cellular pathways, such as the immune response and fatty acid metabolism. As a whole, this thesis presents new insights into the functional effects of perturbagens that could impact neurodegenerative disease pathology and drug discovery.

This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.

This is the first book to assemble the leading researchers in the field of LRRK2 biology and neurology and provide a snapshot of the current state of knowledge, encompassing all major aspects of its function and dysfunction. The contributors are experts in cell biology and physiology, neurobiology, and medicinal chemistry, bringing a multidisciplinary perspective on the gene and its role in disease. The book covers the identification of LRRK2 as a major contributor to the pathogenesis of Parkinson's Disease. It also discusses the current state of the field after a decade of research, putative normal physiological roles of LRRK2, and the various pathways that have been identified in the search for the mechanism(s) of its induction of neurodegeneration.