Neurodegenerative Diseases: Looking Beyond the Boundaries of the Brain

The brain and the body constitute a united wholeness that centuries of scientific positivist reductionism have fragmented into relatively isolated, yet interdependent parts. The conceptualization of neurodegenerative processes has not been immune to this pervasive view. Indeed, traditionally, they are conceived as conditions that begin and end in the intimate, concealed enclosure of the nervous system of an aging human brain. Over the past decades, however, it has become clear, first, that brain neurodegeneration may be relatively silent and long-lasting, likely starting at young adult ages (some even think they are conditioned during gestation). Second, neurodegeneration is preceded and/or accompanied by an ongoing interoceptive disruption that encompasses chronic functional-morphological disturbances along with the cardiovascular, gastrointestinal, and immunological systems. In this scenario, late symptomatic neurodegeneration may, therefore, be the consequence of an ill process that reflects a disruption of the body and brain communication, starting at the periphery, outside the brain.

In support of this assertion, it is now recognized that peripheral inflammation activates inflammatory processes in the central nervous system leading to neurodegeneration. For instance, multiple sclerosis may follow aberrant innate and adaptive immune system cell responses; this association has recently been reported for other neurodegenerative diseases. Furthermore, fluctuations of the cerebral blood flow modify the biophysical coding of neurons and oxidative metabolism. Hence, chronic dysfunctions of the cardiovascular system and irregular blood flow may surely induce long-lasting disruptions of neuronal information processing and increase oxidative stress. Finally, evidence collected over the past twenty years supports the impact that messengers released by the microbiota have on the cognitive and homeostatic functions of the brain. Early onset and sustained dysbiosis, therefore, may contribute significantly to the process of life-long neurodegeneration. These are just a handful of non-neural, peripheral events that could lead to neurodegenerative diseases. With this volume, the editors intend to stimulate and promote the exposure of critical, yet purposeful, reflections that could, on one hand, challenge the conventional views on the etiopathology of neurodegenerative diseases (e.g., proteinopathies) and, on the other, provide new, unexplored avenues to understand them. We truly feel this shift in gears is necessary since we have witnessed the passing of decades, even a century, exploring the old paradigms, but not a single, cornerstone advancement has been made in the direction of curing them, when already installed. Besides regular, aerobic exercising, a healthy diet, and a rich social life as preventive actions or as measures to slowing down the deterioration, we have no other effective means available to counteract or reverse neurodegeneration.

This Research Topic aims at collecting exciting and recent developments looking at neurodegeneration beyond brain boundaries. We particularly encourage the submission of basic research reports, papers on translational studies including early-stage clinical research and thoughtful reviews. Submitted contributions may address, but are not limited to, the following topics:

• Blood leukocytes: trait d’union in neurodegenerative diseases
• Exploring the cardiovascular origin of neurodegeneration
• Etiological contributions of the gastrointestinal tract to neurodegenerative processes

The Editors are looking forward to your provocative contributions.