{"doi":"10.1002/nep3.70010","title":"Targeting peripheral processes to protect the central nervous system","abstract":"Investigating causes of and treatments for neurological diseases originally focused almost exclusively on the central nervous system (CNS). However, a more holistic understanding of neurological diseases emerged in recent years. Contemporary research increasingly considers organs, organ systems, and pathobiological processes outside the CNS as well as their contribution to the course of neurological diseases. Prominent examples are the systemic immunological responses after ischemic, hemorrhagic, or traumatic brain injury1 as well as the gut–brain axis modulating numerous CNS conditions.2, 3 Focusing on the interactions between central and peripheral pathobiological processes may result in a considerable increase of experimental strategy complexity and the necessity for additional research efforts. On the other hand, facing this increased complexity and using more holistic approaches to neurological diseases comes with important advantages. First, we may benefit from a more profound understanding of disease mechanisms and processes modulating the course of CNS diseases. Second, such research could reveal novel therapeutic targets or mechanisms that might be overlooked by exclusively CNS-centered approaches. Third, we may be able to derive novel options for disease prevention, precision diagnosis, and personalized medicine approaches. Fourth, more holistic approaches often require interdisciplinary collaboration, which may in turn inspire out-of-the-box thinking and unconventional solutions to scientific challenges. The current issue of Neuroprotection features articles that put a specific focus on organ system interaction and complex disease mechanisms or were investigating the benefits of non-brain-specific intervention strategies. Thus, the research presented in this issue is meant to make meaningful contributions to achieving a better understanding of CNS disease mechanisms and to developing more effective intervention strategies. Olajide and Ijomone present a review paper summarizing current advances in therapeutic approaches targeting the gut microbiome in neurodegenerative diseases. The work is not restricted to explaining the general impact of a dysbalanced microbiome on neurodegenerative conditions, or the global mechanisms mediating such impact. The review goes further by describing the impact of specific probiotic interventions using living microorganisms to rebalance the gut microbiome. It also focuses on selected species such as Lactobacillaceae and Bifidobacteria, thought to mediate neuroprotective effects. Moreover, the authors provide insights into the influence of the gut microbiome on neuroneogenesis, contributing to recuperation and regeneration in CNS diseases. Finally, the authors describe the beneficial impact of selected bacterial species on conditions such as Parkinson's disease (PD) and Alzheimer's disease (AD), also presenting potential mechanisms by which this beneficial impact is achieved. Therefore, the review contributes to the exploration of novel ways to counter neurodegenerative in such as AD.4 The paper concludes by making meaningful suggestions of potential future research avenues. Neuroinflammation is well known to be a potent contributor to many neurodegenerative diseases,5 as well as a sequel to neuronal injury. Complementing the the work presented by Olajide and Ijomone, the review by Mu and Wang offers detailed insight into the impact of metabolites produced by the gut microbiome on neuroinflammation. A particular focus is set on metabolites recently discovered to modulate neuroinflammation, such as bile acids or indole derivates. The comprehensive review presents detailed information on how the expression of these metabolites is changed in neuroinflammation, as well as how metabolites contribute to neuroinflammatory signaling, and how they enter the CNS or act across the blood-brain barrier (BBB). Mu and Wang also describe how some of these metabolites can be targeted or utilized to exer","journal":"Neuroprotection/Neuroprotection (Chichester, England. 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