Resurrection of neurodegenerative diseases via stem cells

Neurodegenerative diseases (NDDs) are complex disorders that degenerates central nervous system. To this end, we have achieved only palliative treatments and their success is limited. Emerging studies suggest stem cells could be an alternative to recover lost neural network. Transplanting stem cells for replacing damaged neurons is a pivotal step in cell replacement therapies. In this article, NDDs and their pathology, current methods of combating NDDs and potentiality of stem cells in treating NDDs have been reviewed briefly. In addition to this , technical issues that hamper clinical applications of stem cells in creating cellular models and grafted cells for neuron resurrection have been discussed.


INTRODUCTION
Neurodegenerative diseases (NDDs) are devastating disorders with complex etiology. Loss of neurons in the central nervous system, which leads to dementia/ataxia or both is the characteristic feature of NDDs (Sanchez-Mut et al., 2016;Uttara et al., 2009). The pattern in which they occur slightly vary from disease to disease, yet all ultimately culminate to the progressive degeneration of neurons. However, the mechanism which commences this degradation is not clear. Many neurodegenerative diseases are characterized by the aggregation of misfolded/abnormal proteins, along with fibril formation and depositions. The Figure 1 shows the diseases in NDDs and observed pathological proteins (Fig. 1).
These diseases are inexorable and there is a need for exigent solution for this crisis. Inefficacy of present treatments which are solely symptomatic, necessitate alternative approaches to combat with higher efficiency and to provide long term solution.
Phenomenal properties of stem cells and possibility of applications in regenerative medicine, encourages patient-oriented studies in neurodegenerative diseases. Stem cells are considered as cellular models to investigate disease pathology as well as transplantable grafts to recover, to ameliorate and to protect nervous system becomes intriguing research (Abud and Blurton-Jones, 2016;Haston and Finkbeiner, 2016;Wojda and Kuznicki, 2013).
This article aims to address recent advances of stem cells in NDDs for developing disease models and repairing neuron loss. This article will serve as primer to understand potential of stem cells in neurodegenerative resurrection. However, for deep insights on pathology and treatment methodologies, further reading on cited articles is inevitable. Among various neurodegenerative diseases, this article will focus on Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis and Frontotemporal lobar degeneration.  Figure 2 s DDs (Fig. 2)
Grafting of NSCs into the hippocampal regions in AD mouse improved cognition (Blurton-Jones et al., 2009). Human undifferentiated NSCs used for AD treatment in rats (Qu et al., 2001).Transplanted ES cells-derived neurospheres used for AD treatment in mouse (Wang et al., 2006). Human umbilical cord blood mononuclear cells used to treat AD in mice study (Ende et al., 2000). Bone marrow-derived adult progenitor cells (MAPCs) was used to ameliorate AD (Chen et al., 2006).
In drosophila, chaperones such as HSP 70 and drugs such as geldanamycin stimulate the activation of chaperones resulting in the prevention of the loss of dopaminergic neurons (Auluck, 2001).
Homeobox gene Hb9 expression induces mouse ES cells to differentiate to cholinergic motor neuron (Wichterle et al., 2002). MSCs transplantation into the spinal cord to ameliorate ALS (Mazzini et al., 2006) In a mouse model, neurons obtained from human NT-2 cell line (Garbuzova-Davis et al., 2002) and umbilical cord blood cells (Garbuzova-Davis et al., 2003) delayed the progression of ALS.