Resumen de Etiology and Pathogenesis of Parkinson’s Disease
Briana R. de Miranda, J. Timothy Greenamyre
Parkinson’s disease (PD) is a common neurodegenerative disease, affecting an estimated 7 million adults worldwide. The defining features of PD are a set of motor deficits that progressively impair voluntary movement, coupled with non-motor manifestations ranging from olfactory and gastrointestinal dysfunction to dementia. Underlying the motor symptoms is a loss of dopamine input into the basal ganglia, caused by the progressive death of dopamine neurons within the substantia nigra. In addition to dopamine neuron loss, a hallmark pathology of PD is the appearance of proteinaceous Lewy body inclusions in surviving neurons, of which, α-synuclein is a key component. While several genetic mutations have been implicated in the pathology of dopamine neuron death, the majority of PD cases remain idiopathic with no direct link to either genetic mutations or environmental exposures. The newest data connecting etiological risk factors to PD suggest multiple types of cellular dysfunction, as well as a central role of oxidative stress. This chapter examines potential links between highly penetrant monogenic causes of inherited PD and less apparent susceptibility genes that may predispose an individual to developing the disorder. In addition, it considers epidemiological data about exposures to environmental toxins and pathogens and how these relate to research models of PD.
