Recent Research Trends in Neuroinflammatory and Neurodegenerative Disorders

Author:

Cohen Jessica1,Mathew Annette1,Dourvetakis Kirk D.1,Sanchez-Guerrero Estella1,Pangeni Rajendra P.1,Gurusamy Narasimman2ORCID,Aenlle Kristina K.13,Ravindran Geeta4,Twahir Assma1,Isler Dylan1,Sosa-Garcia Sara Rukmini1,Llizo Axel1,Bested Alison C.1,Theoharides Theoharis C.15ORCID,Klimas Nancy G.13,Kempuraj Duraisamy1ORCID

Affiliation:

1. Institute for Neuro-Immune Medicine, Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University, Ft. Lauderdale, FL 33328, USA

2. Department of Pharmaceutical Sciences, Barry and Judy Silverman College of Pharmacy, Nova Southeastern University, Ft. Lauderdale, FL 33328, USA

3. Miami VA Geriatric Research Education and Clinical Center (GRECC), Miami Veterans Affairs Healthcare System, Miami, FL 33125, USA

4. Cell Therapy Institute, Dr. Kiran C. Patel College of Allopathic Medicine, Nova Southeastern University, Ft. Lauderdale, FL 33328, USA

5. Laboratory of Molecular Immunopharmacology and Drug Discovery, Department of Immunology, Tufts University School of Medicine, Boston, MA 02111, USA

Abstract

Neuroinflammatory and neurodegenerative disorders including Alzheimer’s disease (AD), Parkinson’s disease (PD), traumatic brain injury (TBI) and Amyotrophic lateral sclerosis (ALS) are chronic major health disorders. The exact mechanism of the neuroimmune dysfunctions of these disease pathogeneses is currently not clearly understood. These disorders show dysregulated neuroimmune and inflammatory responses, including activation of neurons, glial cells, and neurovascular unit damage associated with excessive release of proinflammatory cytokines, chemokines, neurotoxic mediators, and infiltration of peripheral immune cells into the brain, as well as entry of inflammatory mediators through damaged neurovascular endothelial cells, blood–brain barrier and tight junction proteins. Activation of glial cells and immune cells leads to the release of many inflammatory and neurotoxic molecules that cause neuroinflammation and neurodegeneration. Gulf War Illness (GWI) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) are chronic disorders that are also associated with neuroimmune dysfunctions. Currently, there are no effective disease-modifying therapeutic options available for these diseases. Human induced pluripotent stem cell (iPSC)-derived neurons, astrocytes, microglia, endothelial cells and pericytes are currently used for many disease models for drug discovery. This review highlights certain recent trends in neuroinflammatory responses and iPSC-derived brain cell applications in neuroinflammatory disorders.

Publisher

MDPI AG

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