Astrocytes in Pathogenesis of ALS Disease and Potential Translation into Clinic

Abstract

Astrocytes are the major cell population in the central nervous system (CNS) and play pivotal role in CNS homeostasis and functionality. Malfunction of astrocytes were implicated in multiple neurodegenerative diseases and disorders, including amyotrophic lateral sclerosis (ALS), spinal cord injury (SCI), brain stroke, Parkinson's disease (PD), and Alzheimer disease (AD). These new insights led to the rationale that transplantation of healthy and functional human astrocytes could support survival of neurons and be of therapeutic value in treating neurodegenerative diseases. Here, we will mainly focus on the role of astrocytes in ALS disease, the major cell sources for generation of human astrocytes, or astrocyte like cells and show how multiple preclinical studies demonstrate the efficacy of these cells in animal models. In addition, we will cover immerging early stage clinical trials that are currently being conducted using human astrocytes or human astrocyte like cell population.

Senolytics: A Novel Strategy for Neuroprotection in ALS?

“…The SASP can create a positive feedback loop to increase further pro-inflammatory mediators from the already-senescent cells while spreading inflammation and neurodegeneration to neighboring cells [ 26 ]. This relationship is evident in ALS, where astrocytes secrete toxic soluble factors including proinflammatory signaling molecules TNF-α [ 34 ], TGF-β, IL-6, IFN-γ, and nitric oxide [ 35 ] and overexpress the astrocytic proinflammatory marker C3 in human spinal cord and motor cortex, which has been correlated with the onset of ALS-associated symptoms in the SOD1 G93A mouse model of ALS [ 36 ].…”