http://www.e-sciencecentral.org/articles/SC000020323
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Abstract
Neurological
diseases such as Alzheimer, Parkinson, and ischemic stroke have
increased in occurrence and become important health issues throughout
the world. There is currently no effective therapeutic strategy for
addressing neurological deficits after the development of these major
neurological disorders. In recent years, it has become accepted that
adult neural stem cells located in the subventricular and subgranular
zones have the ability to proliferate and differentiate in order to
replace lost or damaged neural cells. There have been many limitations
in the clinical application of both endogenous and exogenous
neurogenesis for neurological disorders. However, many studies have
investigated novel mechanisms in neurogenesis and have shown that these
limitations can potentially be overcome with appropriate stimulation and
various approaches. We will review concepts related to possible
therapeutic strategies focused on the perspective of neurogenesis for
the treatment of patients diagnosed with Alzheimer disease, Parkinson
disease, and ischemic stroke based on current reports.
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INTRODUCTION
As the aging population increases, common
neurological disorders including Alzheimer disease (AD), Parkinson
disease (PD), and ischemic stroke (IS) have increased and become
important health issues with increasing socioeconomic burdens throughout
the world [1].
The clinical characteristics of AD are related to
progressive memory loss and cognitive deterioration. The
neuropathological traits of AD are massive neuronal death with senile
plaques, which are formed by the aggregation of amyloid-β (Aβ) peptides,
and neurofibrillary tangles, which form from abnormal
hyperphosphorylation of cytoskeletal tau protein [2,3]. These pathological changes in the brains of AD patients represent important targets for diagnosis and treatment [3].
The motor symptoms and mechanisms of PD are well
known, including age-dependent uncontrollable tremors, postural
imbalance, and slowness of movement and rigidity which are caused by the
degeneration of dopaminergic neurons in the substantia nigra pars
compacta (SNc) located in the midbrain [4].
The neuropathological hallmarks of PD are eosinophilic intracellular
inclusion bodies termed Lewy-bodies, and argyrophilic processes (Lewy
neurites) [5].
The pathophysiology of IS is provoked by a reduction
or complete blockage in blood supply to the brain, leading to
dysfunction in the ischemic area [6].
The main causes of ischemia are thrombosis, embolism, systemic
hypoperfusion, or lacunar infarction from small vessel disease. Various
neurologic deficits remain after IS attacks.
There is currently no effective therapeutic strategy
for addressing the neurological deficits after the development of these
major neurological disorders. However, adult neurogenesis has become a
topic of interest, since it was reported that the brain has the
capability to generate new neurons from self-renewing and multipotent
adult neural stem cells (NSCs) placed in the subventricular zone (SVZ)
and subgranular zone (SGZ) of the dentate gyrus [7-11].
Therefore, the objective of this review is to evaluate possible
therapeutic neurogenesis strategies for the treatment of neurological
deficits in patients diagnosed with AD, PD, and IS.
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