Astrocytes as a Potential Target for Alzheimer's Therapies
The brain is made up of far more than just neurons; its functions and complex structures require the support of a wide range of specialized cells types. Prominent amongst these supporting cells are the astrocytes. You might recall research from a few months back that indicated a role for age-related changes in astrocytes in the progression of Alzheimer's disease. Following on from that, researchers here report on the use of gene therapy to target astrocytes and potentially reduce the scope of any harmful behavior:
Astrocytes are the most abundant cell type in the brain and play a critical role in maintaining healthy nervous tissue. In Alzheimer's disease (AD) and most other neurodegenerative disorders, many astrocytes convert to a chronically "activated" phenotype characterized by morphologic and biochemical changes that appear to compromise protective properties and/or promote harmful neuroinflammatory processes.Activated astrocytes emerge early in the course of AD and become increasingly prominent as clinical and pathological symptoms progress, but few studies have tested the potential of astrocyte-targeted therapeutics in an intact animal model of AD. Here, we used adeno-associated virus (AAV) vectors containing the astrocyte-specific Gfa2 promoter to target hippocampal astrocytes [in] mice. AAV-Gfa2 vectors drove the expression of VIVIT, a peptide that interferes with [a signaling pathway] shown by our laboratory and others to orchestrate biochemical cascades leading to astrocyte activation.
After several months of treatment with Gfa2-VIVIT, [the] mice exhibited improved cognitive and synaptic function, reduced glial activation, and lower amyloid levels. The results confirm a deleterious role for activated astrocytes in AD and lay the groundwork for exploration of other novel astrocyte-based therapies.