Search

Parkinson's disease (PD) and Amyotrophic lateral sclerosis (ALS) are neurological disorders pathologically characterized by chronic degeneration of dopaminergic neurons and motor neurons, respectively. There is still no cure or effective treatment against the disease progression and most of the treatments are symptomatic. The present review offers an overview of the different factors involved in the pathogenesis of these diseases. Subsequently, we focused on the recent advanced studies of dietary polyphenols and stem cell therapies, which have made it possible to slow down the progression of neurodegeneration. To date, stem cells and different polyphenols have been used for the directional induction of neural stem cells into dopaminergic neurons and motor neurons. We have also discussed their involvement in the modulation of different signal transduction pathways and growth factor levels in various in vivo and in vitro studies. Likewise stem cells, polyphenols also exhibit the potential of neuroprotection by their anti-apoptotic, anti-inflammatory, and anti-oxidant properties regulating the growth factors levels and molecular signaling events. Overall this review provides a detailed insight into recent strategies that promise the use of polyphenol with stem cell therapy for the possible treatment of PD and ALS., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Alzheimer's and Parkinson's are the two most rampant neurodegenerative disorders worldwide. Existing treatments have a limited effect on the pathophysiology but are unable to fully arrest the progression of the disease. This is due to the inability of these therapeutic molecules to efficiently cross the blood-brain barrier. We discuss how nanotechnology has enabled researchers to develop novel and efficient nano-therapeutics against these diseases. The development of nanotized drug delivery systems has permitted an efficient, site-targeted, and controlled release of drugs in the brain, thereby presenting a revolutionary therapeutic approach. Nanoparticles are also being thoroughly studied and exploited for their role in the efficient and precise diagnosis of neurodegenerative conditions. We summarize the role of different nano-carriers and RNAi-conjugated nanoparticle-based therapeutics for their efficacy in pre-clinical studies. We also discuss the challenges underlying the use of nanomedicine with a focus on their route of administration, concentration, metabolism, and any toxic effects for successful therapeutics in these diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Parkinson's disease is the second most common neurodegenerative disorder characterized by persistent loss of dopaminergic neurons in the SN and clinically associated with cognitive, behavioral and motor deficits. There is an enormous amount of data that provides convincing evidence about the prime involvement of mitochondria in the onset and progression of neurodegeneration. Several studies have also emphasized that accumulation of toxic protein and their aggregates in mitochondria lead to energy deficits, excessive ROS generation, mutations in mitochondrial genome and proteins regulating mitochondrial homeostasis, and impaired mitochondrial dynamics in animal models of PD and patients. Here we discuss about the bioenergetic agents, which have been tested for reducing the mitochondrial dysfunction and associated disease pathology in cellular and animal models of PD and PD patients with encouraging outcomes. We also provide a succinct overview of current therapeutic implications of PGC-1α, SIRT, AMPK, and Nrf2-ARE as salutary targets to overcome the deleterious effects posed by mitochondrial dysfunction in the onset and progression of PD.

Substantial evidence from both genetic and toxin induced animal and cellular models and postmortem human brain tissue indicates that mitochondrial dysfunction plays a central role in pathophysiology of the neurodegenerative disorders including Parkinson's disease (PD), and Huntington's disease (HD). This review discusses the emerging understanding of the role of mitochondrial dysfunction including bioenergetics defects, mitochondrial DNA mutations, familial nuclear DNA mutations, altered mitochondrial fusion/fission and morphology, mitochondrial transport/trafficking, altered transcription and increased interaction of pathogenic proteins with mitochondria in the pathogenesis of PD and HD. This review recapitulates some of the key therapeutic strategies applied to surmount mitochondrial dysfunction in these debilitating disorders. We discuss the therapeutic role of mitochondrial bioenergetic agents such as creatine, Coenzyme-Q10, mitochondrial targeted antioxidants and peptides, the SIRT1 activator resveratrol, and the pan-PPAR agonist bezafibrate in toxin and genetic cellular and animal models of PD and HD. We also summarize the phase II-III clinical trials conducted using some of these agents. Lastly, we discuss PGC-1α, TORC and Sirtuins as potential therapeutic targets for mitochondrial dysfunction in neurodegenerative disorders. This article is part of a Special Issue entitled 'Mitochondrial function and dysfunction in neurodegeneration'., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Parkinson's disease (PD) is a progressive and chronic neurodegenerative disorder, characterized by progressive loss of dopaminergic neurons in substantia nigra. The etiology and pathogenesis of PD is still elusive, however, a large body of evidence suggests a prominent role of oxidative stress, inflammation, apoptosis, mitochondrial dysfunction and proteosomal dysfunction in the pathogenesis of PD. Due to multifactorial nature of the disease, currently available drug therapy cannot halt / slow down the disease progression, and only provides symptomatic relief. Peroxisome proliferator-activated receptor (PPAR), a member of nuclear receptor superfamily, regulates development, tissue differentiation, inflammation, mitochondrial function, wound healing, lipid metabolism and glucose metabolism. Recently, several PPAR agonists were shown to exert neuroprotective activity against oxidative damage, inflammation and apoptosis in several neurodegenerative disorders including Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis and multiple sclerosis. Similarly, regular intake of PPAR activating non-steroidal anti-inflammatory drugs such as indomethacin and ibuprofen was associated with reduced incidence and progression of neurodegenerative disorders in several epidemiological studies. In this article, we review studies relating to the neuroprotective effect of PPAR agonists in in vitro and in vivo models of PD. Similarly, the pharmacological mechanism in neuroprotective actions of PPAR agonists is also reviewed. In conclusion, PPAR agonists exert neuroprotective actions by regulating the expression of a set of genes involved in cell survival processes, and could be a therapeutic target in debilitating neurodegenerative illnesses such as PD.