Neuroinflammation and Neurodegenerative Diseases

Abstract

Neuroinflammation has long been associated with many neurodegenerative diseases (NDDs). Immune-related genetic and environmental risk factors have recently been identified for NDDs, suggesting that neuroinflammation can play an active role in modifying NDD pathologies. Immune cells that underlie this neuroinflammatory response can have both beneficial and detrimental roles in NDDs. These cells can engage in clearance of debris and provide important survival factors to neighboring neurons. However, these cells can also release inflammatory molecules that promote oxidative stress and excitotoxic damage in surrounding neurons, and aberrantly clear healthy cells and structures from the brain. In turn, the cells within the brain play important roles in determining the phenotype and function of these immune cells, and changes in the interaction among these cells in the context of disease can lead to detrimental immune cell activation. There has been recent interest in developing inflammation-related biomarkers to help diagnose NDDs and immune-targeted therapeutics.

Novel Therapeutic Target for Prevention of Neurodegenerative Diseases: Modulation of Neuroinflammation with Sig-1R Ligands

“…Chronic neuroinflammation (elevated and prolonged immune response) is characteristic in NDDs [10,11]. Microglia, astrocytes, endothelial cells, and peripheric immune cells communicate by cytokines and chemokines, causing a prolonged proinflammatory state of microglia, opening of the blood-brain barrier and penetration of the immune cells into the CNS [12,13].…”

Cytotoxicity Profiles and Neuroprotective Properties of the Novel Ifenprodil Analogues as Sigma Ligands

“…Alzheimer's disease (AD), Parkinson's disease (PD), Huntington disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS) are the most common NDDs and the second leading cause of death worldwide in 2016 [3]. The etiopathogenesis of NDD is quite heterogeneous, and structural alterations as well as pathologically altered proteins are associated with selective dysfunctions of neurotransmitter pathways (in particular acetylcholine and dopamine systems) and progressive loss of synapses and neurons [4][5][6].…”

“…1 H-NMR (400 MHz, CDCl 3 ): δ 7.33-7.15 (m, 10H, arom. ), 4.81 (d, J = 4.4 Hz, 1H, CHOH), 2.80 (qd, J = 6.9, 4.0 Hz, 1H, CHCH 3 ), 2.62 (t, J = 7 4. Hz, 2H, NCH 2 CH 2 CH 2 CH 2 ), 2.51-2.31 (m, 2H, NCH 2 CH 2 CH 2 CH 2 ), 2.24 (s, 3H, NCH 3 ), 1.67-1.44 (m, 4H, NCH 2 CH 2 CH 2 CH 2 ), 1.27 (s, 1H, OH), 0.86 (d, J = 6.8 Hz, 3H, CH 3 ).…”