Alzheimers Disease and Neural Transplantation as Prospective Cell Therapy

Abstract

It has long been recognised that Alzheimer's disease (AD) patients present an irreversible decline of cognitive functions as consequence of cell deterioration in the forebrain cholinergic projection system (FCPS), particularly, in a structure called nucleus basalis of Meynert (nbM). The reduction of the number of cholinergic cells in the FCPS disrupts not just its functions and direct connexions but also the modulation of other systems causing interference in several aspects of behavioural performance including arousal, attention, learning and emotion. It is also common knowledge that AD is an untreatable degenerative disease with very few temporary and palliative drug therapies. Neural stem cell (NSC) grafts present a potential and innovative strategy for the treatment of many disorders of the central nervous system including AD, with the possibility of providing a more permanent remedy than present drug treatments. After grafting, these cells have the capacity to migrate to lesioned regions of the brain and differentiate into the necessary type of cells that are lacking in the diseased brain, supplying it with the cell population needed to promote recovery. The present article aims to review the main aspects of Alzheimer's disease and to explore the use of neural stem cells grafts as alternative treatment for the consequent functional deterioration.

ABC transporters, neural stem cells and neurogenesis – a different perspective

“…However, because curing AD requires the complete construction of the damaged neural circuitry, it will be an especially challenging task to induce NSCs to differentiate into a certain cell-type, highlighting a crucial need for developing the ability to control and predict NSC differentiation. It has already been shown that human NSCs transplanted into aged rat brains can differentiate into neural cells and significantly improve the cognitive functions of these animals, further pointing to NSCs as a promising candidate for neuro-replacement therapies [16,17,181]. If new bio-imaging technologies could allow an early diagnosis of the onset of AD when the loss of cholinergic neurons has just begun, it might be possible to restore the generation of cholinergic neurons through the transplantation of NSCs, which would provide a potential remedy for the treatment of this disease.…”

“…For instance, their self-renewing ability would be useful for the treatment of neurodegenerative diseases such as Parkinson's disease (PD) and Alzheimer's disease (AD). Since stem cells and their differentiation products are potentially of broad therapeutic uses, efforts that would enable the supply of a continual source of primitive stem cells in vitro will be vital in revolutionizing the treatment of many diseases [16][17][18].…”

Embryonic Stem Cell in the Therapy of Neurodegenerative Diseases

“…Current treatment strategies for AD include targeting cholinergic and glutamatergic neurotransmission, moderating the -secretase to generate non-toxicamyloid(A ) fragment and delivering NGF into brain which can alleviate symptoms, while these treatments cannot delay or halt the loss and degeneration of neurons in AD brains (van Marum, 2008). Moreover, it has been recognized that the irreversible decline of cognitive functions was related to neuron loss in the forebrain cholinergic projection system: especially in nucleus basalis of Meynert(nbM) where a massive extracellular deposition of A protein occurs in the later stages of the disease (Boncristiano et al;Oliveira & Hodges, 2005). The development of stem cell biology make it a promising treat approach for AD sufferers to restore the lost neurons.…”

System approaches reveal the molecular networks involved in neural stem cell differentiation

“…They play essential roles in repairing and maintaining normal CNS cells. Besides, tissue engineering by normal NSCs transplantation also enables the clinical therapeutic applications for CNS regressive diseases, such as Alzheimer's, Parkinson's, Huntington's disease and other CNS disorders (Storch and Schwarz, 2002;Lee et al, 2005;Oliveira and Hodges, 2005;Sanberg, 2007;Tang et al, 2008;Moghadam et al, 2009;Zhongling et al, 2009;Makri et al, 2010).…”