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Parkinson's Research Studies

Parkinson's Research Studies

The following is a list of Parkinson's research studies:

1.  Friedman, J. H., Brown, R. G., Comella, C., Garber, C. E., Krupp, L. B., Lou, J. S., ... & Taylor, C. B. (2007). Fatigue in Parkinson's disease: a review. Movement Disorders, 22(3), 297-308. Abstract conclusion: Fatigue is a common problem in Parkinson's disease (PD), often the most troubling of all symptoms. It is poorly understood, generally under-recognized, and has no known treatment. This article reviews what is known about the symptom, putting it into the context of fatigue in other disorders, and outlines a program for developing better understanding and therapy.

2.  Moon, H. E., & Paek, S. H. (2015). Mitochondrial dysfunction in Parkinson's disease. Experimental neurobiology, 24(2), 103-116. Abstract conclusions: Parkinson's disease (PD) is characterized by the selective loss of dopaminergic neurons of the substantia nigra pars compacta (SNc) with motor and nonmotor symptoms. Defective mitochondrial function and increased oxidative stress (OS) have been demonstrated as having an important role in PD pathogenesis, although the underlying mechanism is not clear. The etiopathogenesis of sporadic PD is complex with variable contributions of environmental factors and genetic susceptibility. Both these factors influence various mitochondrial aspects, including their life cycle, bioenergetic capacity, quality control, dynamic changes of morphology and connectivity (fusion, fission), subcellular distribution (transport), and the regulation of cell death pathways. Mitochondrial dysfunction has mainly been reported in various non-dopaminergic cells and tissue samples from human patients as well as transgenic mouse and fruit fly models of PD. Thus, the mitochondria represent a highly promising target for the development of PD biomarkers.

3.  Liu, J., & Ames, B. N. (2005). Reducing mitochondrial decay with mitochondrial nutrients to delay and treat cognitive dysfunction, Alzheimer's disease, and Parkinson's disease. Nutritional neuroscience, 8(2), 67-89. Abstract conclusion: Mitochondrial decay due to oxidative damage is a contributor to brain aging and age-related neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD). One type of mitochondrial decay is oxidative modification of key mitochondrial enzymes. Enzyme dysfunction, that is due to poor binding of substrates and coenzymes may be ameliorated by supplementing adequate levels of substrates or coenzyme precursors. Such supplementation with mitochondrial nutrients (mt-nutrients) may be useful to prevent or delay mitochondrial decay, thus prevent or treat AD and PD. In the present review, we survey the literature to identify mt-nutrients that can (1) protect mitochondrial enzymes and/or stimulate enzyme activity by elevating levels of substrates and cofactors; (2) induce phase-2 enzymes to enhance antioxidant defenses; (3) scavenge free radicals and prevent oxidant production in mitochondria, and (4) repair mitochondrial membrane. Then, we discuss the relationships among mt-nutrient deficiency, mitochondrial decay, and cognitive dysfunction, and summarize available evidence suggesting an effect of mt-nutrient supplementation on AD and PD. It appears that greater effects might be obtained by longer-term administration of combinations of mt-nutrients. Thus, optimal doses of combinations of mt-nutrients to delay and repair mitochondrial decay could be a strategy for preventing and treating cognitive dysfunction, including AD and PD.
 

4.  Winklhofer, K. F., & Haass, C. (2010). Mitochondrial dysfunction in Parkinson's disease. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease. 1802(1), 29-44. Abstract conclusion: Mitochondria are highly dynamic organelles which fulfill a plethora of functions. In addition to their prominent role in energy metabolism, mitochondria are intimately involved in various key cellular processes, such as the regulation of calcium homeostasis, stress response and cell death pathways. Thus, it is not surprising that an impairment of mitochondrial function results in cellular damage and is linked to aging and neurodegeneration. Many lines of evidence suggest that mitochondrial dysfunction plays a central role in the pathogenesis of Parkinson's disease (PD), starting in the early 1980s with the observation that an inhibitor of complex I of the electron transport chain can induce parkinsonism. Remarkably, recent research indicated that several PD-associated genes interface with pathways regulating mitochondrial function, morphology, and dynamics. In fact, sporadic and familial PD seem to converge at the level of mitochondrial integrity.

5.  Luo, Y., Hoffer, A., Hoffer, B., & Qi, X. (2015). Mitochondria: A Therapeutic Target for Parkinson’s Disease?. International journal of molecular sciences, 16(9), 20704-20730. Abstract conclusion: In this review, we summarize some of the recent evidence supporting that impairment of mitochondrial dynamics, mitophagy and mitochondrial import occurs in cellular and animal PD models and disruption of these processes is a contributing mechanism to cell death in dopaminergic neurons. We also summarize mitochondria-targeting therapeutics in models of PD, proposing that modulation of mitochondrial impairment might be beneficial for drug development toward treatment of PD.

6.  Golpich, M., Amini, E., Mohamed, Z., Azman Ali, R., Mohamed Ibrahim, N., & Ahmadiani, A. (2016). Mitochondrial Dysfunction and Biogenesis in Neurodegenerative diseases: Pathogenesis and Treatment. CNS Neuroscience & Therapeutics. Abstract conclusion: Several lines of pathological and physiological evidence reveal that impaired mitochondrial function and dynamics play crucial roles in aging and pathogenesis of neurodegenerative diseases. As mitochondria are the major intracellular organelles that regulate both cell survival and death, they are highly considered as a potential target for pharmacological-based therapies. The purpose of this review was to present the current status of our knowledge and understanding of the involvement of mitochondrial dysfunction in pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS) and the importance of mitochondrial biogenesis as a potential novel therapeutic target for their treatment. Likewise, we highlight a concise overview of the key roles of mitochondrial electron transport chain (ETC.) complexes as well as mitochondrial biogenesis regulators regarding those diseases.

7.  Hu, Q., & Wang, G. (2016). Mitochondrial dysfunction in Parkinson’s disease. Translational Neurodegeneration, 5(1), 14. Abstract conclusion: Although the cause of PD is still unclear, the remarkable advances have been made in understanding the possible causative mechanisms of PD pathogenesis. Numerous studies showed that dysfunction of mitochondria may play key roles in DA neuronal loss. Both genetic and environmental factors that are associated with PD contribute to mitochondrial dysfunction and PD pathogenesis. The induction of PD by neurotoxins that inhibit mitochondrial complex I provides direct evidence linking mitochondrial dysfunction to PD. Decrease of mitochondrial complex I activity is present in PD brain and in neurotoxin- or genetic factor-induced PD cellular and animal models. Moreover, PINK1 and parkin, two autosomal recessive PD gene products, have important roles in mitophagy, a cellular process to clear damaged mitochondria. PINK1 activates parkin to ubiquitinate outer mitochondrial membrane proteins to induce a selective degradation of damaged mitochondria by autophagy. In this review, we summarize the factors associated with PD and recent advances in understanding mitochondrial dysfunction in PD.

8.  Jenner, P., & Olanow, C. W. (1998). Understanding cell death in Parkinson's disease. Annals of neurology, 44(S1), S72-S84. Abstract conclusion: Oxidative damage occurs in the brain in PD, as shown by increased lipid peroxidation and DNA damage in the substantia nigra. Increased protein oxidation is also apparent, but this occurs in many areas of the brain and raises the specter of a more widespread pathologic process occurring in PD to which the substantia nigra is particularly vulnerable. The inability of the substantia nigra to handle damaged or mutant (eg, alpha-synuclein) proteins may lead to their aggregation and deposition and to the formation of Lewy bodies. Indeed, Lewy bodies stain for both alpha-synuclein and nitrated proteins. Current evidence enables us to hypothesize that a failure to process structurally modified proteins in regions of the brain exhibiting oxidative stress is a cause of both familial and sporadic PD.

9.  Friedman, J. H., Beck, J. C., Chou, K. L., Clark, G., Fagundes, C. P., Goetz, C. G., ... & Lou, J. S. (2016). Fatigue in Parkinson's disease: report from a mutidisciplinary symposium. NPJ Parkinson's disease, 2. Abstract conclusion: Fatigue is a severe problem for many people living with Parkinson's disease (PD). Best estimates suggest that more than 50% of patients experience this debilitating symptom. Little is known about its etiology or treatment, making the understanding of fatigue a true unmet need. As part of the Parkinson's Disease Foundation Community Choice Research Program, patients, caregivers, and scientists attended a symposium on fatigue on 16 and 17 October 2014. We present a summary of that meeting, reviewing what is known about the diagnosis and treatment of fatigue, its physiology, and what we might learn from multiple sclerosis (MS), depression, and cancer—disorders in which fatigue figures prominently too.

10.  Friedman, J. H. (2009). Fatigue in Parkinson’s disease patients. Current treatment options in neurology, 11(3), 186-190. Abstract conclusion: Nonmotor features of Parkinson’s disease (PD) have only recently been getting the attention they deserve. Dementia, depression, and psychosis are often more devastating than motor dysfunction. Fatigue affects about half of all PD patients and has a major impact on quality of life. Fatigue is the single most important reason cited for medical disability insurance claims by PD patients in the United States. PD patients suffer from both physical and mental fatigue, described as both qualitatively and quantitatively different from the fatigue experienced prior to disease onset. Although fatigue is an early symptom and may be associated with depression, most PD patients with fatigue are not depressed. It is not associated with motor dysfunction but seems to worsen with disease progression. No physiologic differences have been found between fatigued and nonfatigued PD patients. The mechanism of fatigue in PD is unknown. It does not respond to treatment of the motor symptoms. Unlike physical fatigue in normal patients, PD patients often report that their fatigue improves with exercise. No treatment is known to be effective. Methylphenidate was reported to be beneficial in one study, whereas modafinil was not.

11.  Dodson, M. W., & Guo, M. (2007). Pink1, Parkin, DJ-1 and mitochondrial dysfunction in Parkinson's disease. Current opinion in neurobiology, 17(3), 331-337. Abstract conclusion: Mutations in PARKIN, PTEN-induced kinase 1 (PINK1) and DJ-1 are found in autosomal recessive forms and some sporadic cases of Parkinson's disease. Recent work on these genes underscores the central importance of mitochondrial dysfunction and oxidative stress in Parkinson's disease. In particular, pink1 and parkin loss-of-function mutants in Drosophila show similar phenotypes, and pink1 acts upstream of parkin in a common genetic pathway to regulate mitochondrial function. DJ-1 has a role in oxidative stress protection, but a direct role of DJ-1 in mitochondrial function has not been fully established. Importantly, defects in mitochondrial function have also been identified in patients who carry both PINK1 and PARKIN mutations, and in those who have sporadic Parkinson's disease.

12.  Abramov, A. Y., Gegg, M., Grunewald, A., Wood, N. W., Klein, C., & Schapira, A. H. V. (2011). Bioenergetic consequences of PINK1 mutations in Parkinson disease. PLoS One, 6(10), e25622. Abstract conclusion: The purpose of this study was to determine whether cells derived from PD patients with a range of PINK1 mutations demonstrate similar defects of mitochondrial function, whether the nature and severity of the abnormalities vary between mutations and correlate with clinical features. The results provide insight into the molecular pathology of PINK1 mutations in PD and also confirm the critical role of substrate availability in determining the biochemical phenotype – thereby offering the potential for novel therapeutic strategies to circumvent these abnormalities.
 
13.  Exner, N., Lutz, A. K., Haass, C., & Winklhofer, K. F. (2012). Mitochondrial dysfunction in Parkinson's disease: molecular mechanisms and pathophysiological consequences. The EMBO journal, 31(14), 3038-3062. Abstract conclusion: Mitochondrial dysfunction has long been implicated in the etiopathogenesis of Parkinson's disease (PD), based on the observation that mitochondrial toxins can cause parkinsonism in humans and animal models. Substantial progress towards understanding the role of mitochondria in the disease process has been made by the identification and characterization of genes causing familial variants of PD. Studies on the function and dysfunction of these genes revealed that various aspects of mitochondrial biology appear to be affected in PD, comprising mitochondrial biogenesis, bioenergetics, dynamics, transport, and quality control.
 
14.  Morris, G., Berk, M., Walder, K., & Maes, M. (2015). Central pathways causing fatigue in neuro-inflammatory and autoimmune illnesses. BMC medicine, 13(1), 28. Abstract conclusion: Many patients suffering from neuroinflammatory and autoimmune diseases, such as multiple sclerosis, Parkinson’s disease and systemic lupus erythematosus, also commonly suffer from severe disabling fatigue. Such patients also present with chronic peripheral immune activation and systemic inflammation in the guise of elevated proinflammtory cytokines, oxidative stress and activated Toll-like receptors. This is also true of many patients presenting with severe, apparently idiopathic, fatigue accompanied by profound levels of physical and cognitive disability often afforded the non-specific diagnosis of chronic fatigue syndrome.
 
 
 
 
 
 

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