Targeting NGF-pathway for developing neuroprotective therapies for multiple sclerosis and other neurological diseases

Abstract

Inflammation is the first line of defense against injury and infection and works both by controlling the ongoing pathological processes and by promoting neuroprotection and regeneration. When the inflammatory response is hyperactivated, it plays a pivotal role in the pathophysiology of many neurological diseases, as it can also be a source of additional injury to host cells. Since neurons lack the ability to divide and recover poorly from injury, they are extremely vulnerable to autodestructive immune and inflammatory processes, and this side effect is fundamental to the outcome of neurological diseases. Inappropriate immune responses are responsible for diseases such as Multiple Sclerosis (MS), Alzheimer’s disease (AD) or Parkinson’s disease (PD) and for the increased disability after brain trauma or stroke. However, in certain circumstances immune responses in the brain might have a neuroprotective effect, possibly mediated by the release of trophic factors from inflammatory and/or glial cells. The nerve growth factor (NGF) was the first neurotrophin discovered for its stimulatory effect on differentiation, survival, and growth of neurons in peripheral and central nervous system. This factor can protect axons and myelin from inflammatory damage and also can modulate the immune system, reducing the enhanced excitotoxicity during
acute inflammatory activation. Therefore, because its neuroprotective activity and immunomodulatory effects, NGF may represent a new therapeutic approach for the treatment of numerous brain disorders.