NGF Released from Blood Cells or CollagenHydrogels as a Therapeutic Target in Alzheimer's Disease?

Abstract

Alzheimer's disease (AD) is a severe neurodegenerative disorder of the brain characterized by extracellular beta-amyloid plaques, intraneuronal tau inclusions, vascular impairment, inflammation, neurodegeneration, and memory loss. Acetylcholine is the most important neurotransmitter for memory, and cholinergic neurons selectively degenerate in AD, and a loss of acetylcholine directly correlates with cognitive decline. Nerve growth factor (NGF) is the most potent growth factor to support the survival of these cholinergic neurons. Thus, researchers are interested to deliver NGF directly into the brain to the cholinergic neurons. As the brain is isolated by the blood-brain barrier, the large protein NGF cannot easily pass into the brain, and peripheral administration of NGF also causes severe side effects. Blood cells may represent a potent therapeutic strategy to deliver NGF into the brain. Monocytes can be isolated and loaded with NGF and may transmigrate into the brain. As monocytes are precursors of microglia, they may differentiate and release NGF but also phagocyte and eliminate toxic plaques. Platelets are small anuclear cells and become rapidly activated during vascular lesions, and they may migrate to lesion sites and repair blood vessels and also eliminate toxic beta-amyloid depositions in vessels. In order to guarantee a stable and slow release, the use of biomaterials is of interest, especially collagen hydrogels that may be useful to protect these transmigrating blood cells. In this review, I summarize advantages and challenges of using transmigrating cells to deliver NGF directly into the brain.