About this Research Topic
A wide range of neurodegenerative disorders affect the central nervous system, causing changes in neuronal circuitry, loss in neuronal connections, and eventual neuronal death. The high prevalence of neurodegenerative diseases like Parkinson's disease, Alzheimer's disease, and other degenerative brain disorders in the aging population poses a significant burden on global healthcare systems. Given their highly complex nature, etiologic research on many of these neurodegenerative diseases are often conducted in isolation. However, elucidating conserved mechanistic underpinnings of neurodegenerative diseases could be utilized to develop pan-neurodegenerative treatments/interventions. Is it possible to tease apart the similarities and differences between different neurodegenerative diseases at the molecular, cellular and organismal levels? Could there be common pathophysiological pathways that lead to synaptic loss and neuronal death?
This research topic intends to address these questions broadly and encourages the submission of research findings that could help understand the interplay between different neurodegenerative diseases and uncover novel therapeutic opportunities for neuroprotection during aging. Some examples include:
• Proteotoxicity: Clearance of misfolded proteins and proteostasis, endoplasmic reticulum stress, and the unfolded protein response (e.g., proteasomes, lysosomes, autophagy).
• Mitochondrial function: Mitochondrial mechanisms in Parkinson’s Disease, Huntington’s Disease, and Amyotrophic Lateral Sclerosis (ALS), ataxias and other diseases.
• RNA transcription and processing: Synuclein (Parkinson's), Trinucleotide repeat expansions (Huntington’s, ataxias), hexanucleotide repeat expansion (familial FTD and ALS), TDP43.
• Protein translation deficits: Defects in mRNA localization, mRNA sequestration, ribosome biogenesis, effects of mutant tRNA synthetases.
• Inflammation: Involvement of microglial/astrocytic activation and the innate immune system.
• Adaptive immune responses to neurodegeneration.
• Prion-like spread of pathological proteins: Pathology stemming from distinct “strains” of tau and alpha-synuclein, TDP43, the gut-brain axis.
• Connectomics: Identification of neural cell populations, brain regions, neural circuits, and/or large-scale networks (connectome) that are vulnerable during brain aging and contribute to neurodegeneration.
• Genomics and epigenomics: Identification of genetic and epigenetic contributions to neurodegenerative syndrome and the overlapping phenotypic presentations of individuals with the same genetic mutations. Further, identification of genetic and epigenetic mechanisms that are associated with motor/cognitive decline.
• Neurogenesis or adaptive cell stress response pathways: molecular, cellular, synaptic, and neural circuitry mechanisms underlying brain plasticity.
• Develop and characterize novel animal models of neuropathology.
• Human cell reprogramming approaches: iPSCs, 3D or organoid culture approaches to study molecular, physiological, and systems cell biology.
• Identification of biomarkers that could distinguish different neurodegenerative diseases.
• Clinical correlates of neuroanatomical changes.
• Brain iron accumulation: The relationship between clinical symptoms and brain iron accumulation and comparisons between localization and amount of brain iron accumulation between different neurodegenerative diseases.
• Non-motor symptoms: Sleep and circadian disturbances; Smell (anosmia); cognitive changes.
This research topic intends to address these questions broadly and encourages the submission of research findings that could help understand the interplay between different neurodegenerative diseases and uncover novel therapeutic opportunities for neuroprotection during aging. Some examples include:
• Proteotoxicity: Clearance of misfolded proteins and proteostasis, endoplasmic reticulum stress, and the unfolded protein response (e.g., proteasomes, lysosomes, autophagy).
• Mitochondrial function: Mitochondrial mechanisms in Parkinson’s Disease, Huntington’s Disease, and Amyotrophic Lateral Sclerosis (ALS), ataxias and other diseases.
• RNA transcription and processing: Synuclein (Parkinson's), Trinucleotide repeat expansions (Huntington’s, ataxias), hexanucleotide repeat expansion (familial FTD and ALS), TDP43.
• Protein translation deficits: Defects in mRNA localization, mRNA sequestration, ribosome biogenesis, effects of mutant tRNA synthetases.
• Inflammation: Involvement of microglial/astrocytic activation and the innate immune system.
• Adaptive immune responses to neurodegeneration.
• Prion-like spread of pathological proteins: Pathology stemming from distinct “strains” of tau and alpha-synuclein, TDP43, the gut-brain axis.
• Connectomics: Identification of neural cell populations, brain regions, neural circuits, and/or large-scale networks (connectome) that are vulnerable during brain aging and contribute to neurodegeneration.
• Genomics and epigenomics: Identification of genetic and epigenetic contributions to neurodegenerative syndrome and the overlapping phenotypic presentations of individuals with the same genetic mutations. Further, identification of genetic and epigenetic mechanisms that are associated with motor/cognitive decline.
• Neurogenesis or adaptive cell stress response pathways: molecular, cellular, synaptic, and neural circuitry mechanisms underlying brain plasticity.
• Develop and characterize novel animal models of neuropathology.
• Human cell reprogramming approaches: iPSCs, 3D or organoid culture approaches to study molecular, physiological, and systems cell biology.
• Identification of biomarkers that could distinguish different neurodegenerative diseases.
• Clinical correlates of neuroanatomical changes.
• Brain iron accumulation: The relationship between clinical symptoms and brain iron accumulation and comparisons between localization and amount of brain iron accumulation between different neurodegenerative diseases.
• Non-motor symptoms: Sleep and circadian disturbances; Smell (anosmia); cognitive changes.
Keywords: Parkinson's disease, Neurodegenerative diseases, Alzheimer's disease, Pathophysiological mechanisms, Neuroprotection, Aging, Synaptic loss, Cell death, Neuroimmune interactions
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
