Steering Functional Pathways, Genomic and Non-genomic, to Keep Neurodegeneration in Check

Dear Colleagues,

Neurodegeneration is part and parcel of brain injury and also of brain disorders that are aptly called neurodegenerative diseases, for example, Alzheimer disease and Parkinson disease. Neurodegenerative diseases share a range of molecular and cellular pathologies, including protein aggregation, mitochondrial dysfunction, glutamate toxicity, inadequate glucose supply, energy crisis, calcium imbalance, proteolytic stress, oxidative stress, and neuroinflammation. Thus, efficacious treatment of neurodegeneration appears to require a multifaceted approach. In some detail, such treatment should include targeting programmed cell death of neurons, supportive functions of astrocytes, oligodendrocytes, and endothelial cells, as well as microglial activation as part of the neuroinflammatory/immune response. A handful of approaches appeared to be extraordinarily beneficial when applied to cell cultures, animal models, and some even in clinical studies (raloxifene and hyperbaric oxygen) (review by Veenman, 2020).

Briefly, their effects include modulation of programmed cell death, injury healing, inflammation and infection, cell and tissue regeneration, neurite growth, cell proliferation, cell migration, and differentiation of stem cells, as well as angiogenesis. At molecular biological levels, this includes modulation of metabolic pathways to sustain energy requirements, proteinogenesis, intracellular calcium balance, maintenance of transmitter systems at cell nuclear, cytosolic, and plasma membrane levels, and counteracting deleterious effects of oxidative stress and other radical formations. Molecules that have attracted attention include growth factors, sirtuins, cholesterol, Abeta, and many others. Beneficial effects of such efficacious agents and treatments include genomic as well as non-genomic targets and pathways. Genomic effects can relate to cell nuclear receptor signaling, as well as immediate early genes. Non-genomic effects can include interactions with molecules and receptors at various other intracellular locations.

Papers are sought that deepen our insights into the mechanisms of successful treatments for neurodegeneration.

Dr. Leo Veenman
Guest Editor

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