The invariable loss of these SNpc dopamine neurons and consequent development of dystrophic striatal projections are hallmarks of PD. Characterized clinically by resting tremor, bradykinesia, rigidity and postural instability, the primary locus of disease is the nigrostriatal pathway comprised of pigmented, dopaminergic neurons within the substantia nigra pars compacta (SNpc) and attendant projections to the putamen. Parkinson’s disease (PD) is the second most common neurodegenerative disorder of aging and the most common movement disorder. Here we present our current understanding of PD etiology, pathology, clinical symptoms and therapeutic approaches with an emphasis on misfolded α-synuclein. In fact, PD is both a cerebral amyloid disease and the most common synucleinopathy, that is, diseases that display accumulations of α-synuclein. The presence of toxic aggregated forms of α-synuclein (e.g., amyloid structures) are purported to be a harbinger of subsequent pathology. One common thread in PD is the presence of intracytoplasmic inclusions that contain the protein, α-synuclein.

The combination of methodical clinical evaluation, systematic pathological studies and detailed genetic analyses have revealed that PD is a multifaceted disorder with a wide-range of clinical symptoms and pathology that include regions outside the dopamine system.

Although the exact cause of sporadic PD remains enigmatic studies of familial and rare toxicant forms of this disorder have laid the foundation for genome wide explorations and environmental studies. However, these therapies do not fully treat the clinical syndrome nor do they alter the natural history of this disorder motivating clinicians and researchers to further investigate the clinical phenotype, pathophysiology/pathobiology and etiology of this devastating disease.

Loss of the neurotransmitter dopamine was recognized as underlying the pathophysiology of the motor dysfunction subsequently discovery of dopamine replacement therapies brought substantial symptomatic benefit to PD patients. Parkinson’s disease (PD) is the most common age-related motoric neurodegenerative disease initially described in the 1800’s by James Parkinson as the ‘Shaking Palsy’.

Locked Together by Michelle Abbott