Meeting New Challenges in Translationally Relevant Neurodegenerative Disease Research

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Background

Modern genetic and systems biology advances are propelling neurodegenerative disease research forward at a pace that is both exciting and at times bewildering. Just a few examples of this progress at the genetic level include discovery of Triggering Receptor Expressed on Myeloid cells 2 (TREM2) mutations that cause AD; and alterations in the Chromosome 9 Open Reading Frame 72 (C9orf72) gene which cause intracellular TAR DNA-Binding Protein-43 (TDP-43) inclusions associated with Frontotemporal Lobar Degeneration (FTLD). However, TREM2 mutations are also associated with a frontal dementia with bone cysts; and C9orf72 is a major cause of Amyotrophic Lateral Sclerosis (ALS).



This neurodegenerative complexity is also reflected at the cellular level. For example, there are many genes that cause Spinocerebellar Ataxia (SCA), yet regardless of the causal gene, Purkinje cell loss is particularly prominent. In another case, microtubule-associated protein tau (MAPT) mutations are associated with different diseases that can affect different cell types (e.g., astrocytic tau in cortical basal degeneration and neurofibrillary tangles associated with frontotemporal dementia with Parkinsonism linked to chromosome 17 (FTDP-17).



Thus, little wonder that interplay among specific genetic, cellular, as well as environmental factors (e.g., TBI) often give rise to complex psychological and cognitive disturbances that differ, despite being associated with a common mutant protein (for example, tau in AD and FTD).



Such examples highlight the importance of animal model, bioinformatic, and neuropathological studies that better reflect the clinical realities of the specific disorder researchers focus upon. Increased attention to these factors is significant in enhancing the translational relevance that is needed to facilitate new progress.



Examples for contributions (original research and reviews) that touch upon:

• The role of TDP-43 in neurodegenerative disease.

• Tauopathy studies that touch on behavioral and/or neuropathological distinctions among different disorders.

• Amyloid and tau interactions.

• Alpha-synuclein and interactions with other neuropathologic processes.

• Animal model studies that incorporate more complex behavioral and cognitive features that are relevant to specific disorders.

• Interactions between environmental and genetic factors that influence distinct neurodegenerative symptoms.

• Studies that address vulnerability of certain cell types in the brain to a variety of genetic insults.

Suitable topics are not limited to the examples above. Contributors are encouraged to reach out the editor with any questions.

Keywords: Neurodegeneration, Dementia, Alzheimer's disease, ALS, tauopathy, PTSD, schizophrenia, Parkinson's disease, traumatic brain injury, translational significance, Ataxias, Huntington's Disease

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.

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