Parkinson’s disease is a common neurodegenerative disorder. Pathologically in the majority of cases there are proteinaceous inclusions designated Lewy bodies and neurites composed of aggregates of alpha-synuclein and other proteins. There is widespread neuronal degeneration, but the degeneration of dopamine neurons leads to the characteristic clinical features of slowness of movement, rest tremor, rigidity and postural instability. Accumulation of aggregated alpha-synuclein in other brain regions leads to degeneration of other brain structures and accounts for many of the other symptoms of PD including depression, anxiety, cognitive dysfunction, sleep disturbances and autonomic dysfunction among others.
Although most of PD is thought to be sporadic with no sole contributing factor, a small portion is due to mutations in alpha-synuclein and LRRK2 that cause autosomal dominant PD and mutations in parkin, PINK1 and DJ-1 that cause autosomal recessive PD. Rare mutations in other genes also cause PD and PD related syndromes. Identification of these mutations has provided tremendous insight into the pathogenesis of PD and clues to the underlying causes of sporadic PD. Mitochondrial dysfunction and indices of oxidative stress are important and consistent features of PD. In addition abnormalities in synaptic transmission and abnormal protein accumulation seems to occur early in pathogenesis of PD. We are investigating how genetic causes of PD contribute to mitochondrial and synaptic abnormalities and how oxidative and nitrosative stress contributes to the pathogenesis of PD. New targets for therapeutic intervention are emerging from these investigations.
Dr. Dawson is the Leonard and Madlyn Abramson Professor in Neurodegenerative Diseases and Director of the Institute for Cell Engineering at the Johns Hopkins University School of Medicine. Dr. Dawson elucidated the molecular mechanisms by which glutamate kills neurons through nitric oxide activation of poly [ADP-ribose] (PAR) polymerase (PARP) and release of apoptosis inducing factor (AIF) via PAR polymer and discovered Parthanatos. Dr. Dawson has been at the forefront of research into the biology and pathobiology of mutant proteins linked to familial Parkinson’s disease. These studies are providing novel opportunities for therapies aimed at preventing the degenerative process of PD and other neurodegenerative disorders.
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The National Parkinsons Foundation
For over half a century, the National Parkinson Foundation (NPF) has focused on meeting the needs in the care and treatment of people with Parkinson’s disease (PD).
The Michael J. Fox Foundation for Parkinson's Research
The Michael J. Fox Foundation is dedicated to finding a cure for Parkinson's disease through an aggressively funded research agenda and to ensuring the development of improved therapies for those living with Parkinson's today.
National Institute of Neurological Disorders and Stroke (NINDS)
The mission of the National Institute of Neurological Disorders and Stroke (NINDS) is to reduce the burden of neurological disease. As a part of this mission, the NINDS supports basic, translational and clinical research on Parkinson's disease (PD), a devastating and complex neurodegenerative disorder that progressively impairs the control of purposeful movement.