Astrogliosis - Novel Therapeutic Techniques

Novel Therapeutic Techniques

In response to the destructive causes of astrogliosis, including altered molecular expression, release of inflammatory factors, astrocyte proliferation and neuronal dysfunction, scientists are studying various new ways to treat astrogliosis and neurodegenerative diseases. Astrocytes have been found to play a role in diseases such as Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Parkinson’s disease, and Huntington’s disease. The inflammation caused by reactive astrogliosis augments many neurological diseases. Researchers have begun to study the possible benefits of inhibiting the inflammation caused by reactive gliosis to reduce its neurotoxic effects.

Neurotrophins are currently being researched as possible drugs for neurological protection as they have been found to aid in the restoration of neurological function. For example some studies and clinical trials have used nerve growth factor to regain some cholinergic function in Alzheimer’s disease.

One specific drug candidate is BB14, which is a nerve growth factor-like peptide that acts as a TrkA agonist. This drug, which lessens astrogliosis and its damaging effects, could be used to treat neurological diseases as well as glaucoma, neurotrophic keratitis, and dry eyes. Researchers believe further research into neurotrophins will lead to the development of a highly selective, potent, and small neurotrophin that targets reactive gliosis to alleviate some neurodegenerative diseases.

TGFB is a regulatory molecule involved in proteoglycan production. This production is increased in the presence of bFGF or Interleukin 1. An anti-TGFß antibody may potentially reduce GFAP upregulation after CNS injuries, promoting axonal regeneration.

Injection of ethidium bromide kills all CNS glia (oligodendrocytes and astrocytes), but left axons, blood vessels, and macrophages unaffected. This provides an environment conducive to axonal regeneration for about four days. After four days, CNS glia reinvade the area of injection and axonal regeneration is consequently inhibited. This method has been shown to reduce glial scarring following CNS trauma.

Oligodendrocyte precursor cells and C6 glioma cells produce metalloprotinease, which is shown to inactivate a type of inhibitory proteoglycan secreted by Schwann cells. Consequently, an increase in MMP2 in the environment around axons may facilitate axonal regeneration via degradation of inhibitory molecules due to increased proteolytic activity.