Human-based models to decipher the mechanisms of brain diseases

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Background

Diseases affecting the human brain, including neurodegenerative and infectious diseases, are complex and challenging to treat. The unique operations of neural networks in the human brain, regulated by refined mechanisms of cellular communication between distinct cell populations, turns the development of efficient therapeutic interventions against human brain diseases into an enormous challenge. An example is Alzheimer’s disease, a burgeoning global health problem still in need of conclusive understanding of its molecular basis, and consequently, with no effective therapies available to tackle this condition.

It is therefore clear that deciphering such complexity requires the availability and capability of translational and relevant disease models. Although the insights obtained from non-human experimental models such as rodents are precious, they do not fully capture the molecular and functional neurobiological mechanisms of the human brain in health and disease, which are dependent on the cellular connections formed in vivo. In the past ten years, the use of human tissue-based models has emerged as a promising approach in the understanding of the molecular and cellular mechanisms underlying central nervous system dysfunction and neurodegeneration. In this Research Topic, we will explore a range of alternative and complementary models which are based exclusively on human samples/subjects-based technologies in vivo, in vitro or in silico.

We welcome studies highlighting unique insights and gains from the use of any human models in the study of either chronic or acute conditions affecting the human nervous system, including (but not limited to)

• infections by neurotropic viruses;
• epilepsy;
• Parkinson’s disease, Alzheimer’s disease and other causes of dementia;
• brain cancer;
• the evaluation of the potential of novel neuroprotective agents, as well as liquid biopsies in the search for biomarkers.

Finally, we would also welcome studies highlighting the strengths, limitations and challenges to fully exploit patient-derived models including (but not limited to) brain tissue ex-vivo (live or post-mortem), patient-derived reprogrammed iPSCs models, brain organoids, large clinical and neurogenomics data-sets, in-vivo brain imaging and neurostimulation. The standardizing of live and post-mortem human brain preparation remains a significant challenge and therefore submissions of reports of innovative use of such tissue are encouraged. We will consider Original Research, Methods manuscripts, and Review articles focusing on the advantages and limitations of applying human brain-derived samples or human subjects in the discovery of mechanisms underlying neurological disorders/neuroprotection.

Keywords: Culture, Slices, Human, Surgery, Organoids, Neurodegeneration, In Vitro, Neurospheres, Organotypic slices, Epilepsy

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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