About this Research Topic

Background

Neurological disorders are a diverse group of disorders in the central and peripheral nervous systems and they are becoming a growing burden as society ages. Aging has been shown to alter the brain at molecular, cellular, vasculature, and cognitive level, increasing the risk of cerebral conditions such as tumors, stroke, and neurodegenerative disorders. In the adult brain, a very limited number of stem cells are present, leaving the brain with insufficient self-regenerative capacity against disease-caused damage.

The development of reprogramming and stem cell technology revolutionized the neuroscience field by giving access to donor-specific neural cells. There are multiple stem cell/direct reprogramming-based techniques that help us to recapitulate the disease process in a personalized manner. Many laboratories have adopted an approach that relies on modeling diseases in a dish with induced pluripotent stem cells (iPSCs) and further expanded to the development of organoids—collections of cells that reflect features of whole tissues. An alternative to iPSC reprogramming and differentiation are direct conversion or trans-differentiation strategies, which could maintain the age-associated features of donor cells. Neurons generated with direct conversion (iN), present a unique opportunity to understand how the aging process impacts these cells and can lead to various neurological disorders.

Reprogramming technology also has great therapeutic potential to replenish cell loss in neurological diseases. Terminally differentiated or lineage-committed hiPSCs could be a source of autologous disease-relevant cells used for transplantation therapy without eliciting an immunogenic response. Using genome engineering, patient-specific neural cells with corrected disease mutations could be generated for autologous cell-based gene therapy. Another emerging regenerative strategy is reprogramming of the cell fate in vivo to generate new neurons. In vivo neural reprogramming has achieved impressive progress, ranging from the generation of diverse glia-converted neurons in multiple CNS regions to functional improvements for neurological conditions.

This Research Topic aims to highlight the advances in exploring neurological diseases using human cell reprogramming models, and advance our understanding of the genotypes, phenotypes, and mechanism of action in the brain diseases. We would also like to attract new information related to the variety of reprogramming and stem cell-based therapeutic strategies for neurological diseases.

We particularly welcome submission of Original Research, Review, Methods, and Perspective articles.

This Research Topic focuses on, but not limited, to the following themes

1. Reprogramming-based disease models in brain damage and age-related neural degeneration. Relevant diseases include:
- Age-related degeneration (Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, Dementia, etc.)
- Brain Trauma, Stroke, Tumor, Psychiatric and other neurological disorders
- Reprogramming of different cell types that are affected in degeneration: neurons, astrocytes, oligodendrocytes, microglia
- Inflammation and the extracellular environment in neurodegeneration
- In vivo reprogramming
- Biomaterials and/or drugs for targeting stem cell niches and/or in combination with stem cells.

2. Use of reprogramming approaches as therapeutic agents. Relevant therapeutic strategies include, but are not limited to:
- iPSC and derived stem cells per se, with or without genetic modifications
- Transplantation of directly reprogrammed cells
- In vivo reprogramming
- Biomaterials and/or drugs for targeting stem cell niches and/or in combination with stem cells
- Neuron targeted nanoparticles

3. Drug screening of therapeutics for neurodegeneration and brain injury using reprogramming-based models.

Topic Editor Dr Janelle Drouin-Ouellet is co-inventor of the patent application PCT/EP2018/ 062261 owned by the New York Stem Cell Foundation. The other Topic Editors declare no competing interests with regard to the Research Topic subject.

Keywords: Neurological disorders, Aging, neurodegeneration, Reprogramming, Clinical application, Disease modeling, Stem cell therapy.

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