Astrocyte function and role in motor neuron disease: A future therapeutic target?

Abstract

Astrocytes are the most numerous cell type within the central nervous system (CNS) and perform a variety of tasks, from axon guidance and synaptic support, to the control of the blood brain barrier and blood flow. To perform these roles, there is a great variety of astrocytes. In this review, we summarize the function of astrocytes, in particular, their role in maintaining homeostasis at the synapse, regulating neuronal signaling, protecting neurons from oxidative damage, and determining the fate of endogenous neural precursors. The review also highlights recent developments indicating the role of astrocytes in motor neuron disease (MND), emphasizing their potential as therapeutic targets and agents in cell replacement therapy. The Cu-Zn superoxide dismutase (SOD1) gene that has been implicated in 20% of cases of familial MND must be expressed in the glial cells as well as motor neurons to produce the disease state in murine models of disease. Selectively reducing mutant SOD1 (mSOD1) in astrocytes does not affect disease onset but slows disease progression, whereas reducing mSOD1 in motor neurons delays disease onset and slows early disease but has less effect on life span. This suggests that glial cells represent potential therapeutic targets in MND. However, the lack of specific markers for astrocytes, their precursors, and sub-types means that our knowledge of astrocyte development/differentiation and response to injury lags far behind our understanding of function. Only by filling this knowledge gap can astrocytes be effectively targeted or replaced to successfully treat chronic CNS disorders such as MND.

Neuroimmune Response in Ischemic Preconditioning

“…The pioneering papers in the RIPC field suggest that neuroprotection is induced rapidly [30,31,37]; however, the duration of protection has not been determined [37,38]. Molecular determinants behind the phenomenon of RIPC have not been fully elucidated, but there is some evidence of overlap with molecular mediators of ischemic and LPS preconditioning, including hypoxiainducible factor (HIF)-1α [39], and inflammatory factors [40][41][42][43]. Remote limb ischemia may induce global expression of these molecular mediators of preconditioning that confers protection to multiple organ systems, including the brain.…”

Hu Antigen R (HuR) Is a Positive Regulator of the RNA-binding Proteins TDP-43 and FUS/TLS

“…11). Astrocytes play an important role in CNS homeostasis, including synaptic maintenance, blood-brain barrier and blood flow, neuroprotection, and energy production (48). The broad range of functions is attributable to a versatile molecular phenotype, including the array of factors capable of being secreted, which vary depending on the microenvironment and signals therein (e.g.…”

Angiotensin II and aldosterone-induced neuronal damage in neurons through an astrocyte-dependent mechanism

“…30 However, the contribution of astrocytes to neuronal degeneration has only recently been shown. 3,4 Therefore, we introduced an SGN and astrocyte co-culture model to verify the hypothesis that astrocytes are involved in SGN damage induced by Ang II stimulation.…”