J Neurol Neurosurg Spine | Volume 1, Issue 1 | Review Article | Open Access
Kempuraj D1,2*, Thangavel R1,2, Natteru PA1, Selvakumar GP1, Saeed D1, Zahoor H1, Zaheer S1, Iyer SS1,2 and Zaheer A1,2
1Department of Neurology, Center for Translational Neuroscience, School of Medicine, University of Missouri, Columbia, MO, USA
2Harry S. Truman Memorial Veterans Hospital, Columbia, MO, USA
*Correspondance to: Kempuraj Duraisamy
Fulltext PDFNeurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and Multiple Sclerosis (MS) are characterized by neuronal degeneration and neuronal death in specific regions of the central nervous system (CNS). In AD, neurons of the hippocampus and entorhinal cortex are the first to degenerate, whereas in PD, dopaminergic neurons in the substantia nigra degenerate. MS patients show destruction of the myelin sheath. Once the CNS neurons are damaged, they are unable to regenerate unlike any other tissue in the body. Neurodegeneration is mediated by inflammatory and neurotoxic mediators such as interleukin-1beta (IL-1β), IL-6, IL-8, IL-33, tumor necrosis factor-alpha (TNF-α), chemokine (C-C motif) ligand 2 (CCL2), CCL5, matrix metalloproteinase (MMPs), granulocyte macrophage colony-stimulating factor (GM-CSF), glia maturation factor (GMF), substance P, reactive oxygen species (ROS), reactive nitrogen species (RNS), mast cells-mediated histamine and proteases, protease activated receptor-2 (PAR-2), CD40, CD40L, CD88, intracellular Ca+ elevation, and activation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa-B (NF-kB). Activated microglia, astrocytes, neurons, T-cells and mast cells release these inflammatory mediators and mediate neuroinflammation and neurodegeneration in a vicious manner. Further, immune and inflammatory cells and inflammatory mediators from the periphery cross the defective blood-brain-barrier (BBB) and augment neuroinflammation. Though inflammation is crucial in the onset and the progression of neurodegenerative diseases, anti-inflammatory drugs do not provide significant therapeutic effects in these patients till date, as the disease pathogenesis is not yet clearly understood. In this review, we discuss the possible factors involved in neuroinflammation-mediated neurodegeneration.
Cytokine; Neuroinflammation; Neurodegeneration; Parkinson’s disease
Kempuraj D, Thangavel R, NatteruPA, Selvakumar GP, Saeed D, Zahoor H, et al. Neuroinflammation Induces Neurodegeneration. J Neurol Neurosurg Spine. 2016; 1(1): 1003.