Parkinson’s Disease: Genetics, Mechanisms and Diagnosis

Parkinson’s disease is a complex neurodegenerative disorder, mainly characterized by the loss of dopaminergic neurons in the substantia nigra and their projections to the striatum, causing several motor deficits. Neuronal cytoplasmic inclusions, named Lewy Bodies, are found in the affected areas. Parkinson’s disease is distributed worldwide, affecting all ethnic groups and socioeconomic classes. Protein homeostasis is crucial for preventing neurodegeneration. Misfolding of proteins can lead to loss or gain of function, resulting in protein dysfunction and causing various types of diseases. Five genes containing pathogenic mutations were identified to contribute for incorrect protein conformation in Parkinson’s disease. Mitochondrial dysfunction and purinergic receptor signaling are also involved in the mechanism of disorder. Several types of pharmacological intervention were developed. Dopamine agonists are the most common therapeutic agents used currently. N-methyl-D-aspartate type glutamate receptor antagonist, monoamine oxidases and anticholinergic drugs can be therapeutic alternatives. New techniques and studies have contributed to the discovery of new genes and genetic risk factors for Parkinson’s disease. Brain banks and imaging analyses can also be very useful tools for understanding the mechanisms of disease progression. Current studies on molecular aspects of Parkinson’s disease, together with the development of new drugs, techniques and tests to improve diagnosis accuracy will bring new perspectives for PD therapies.

Keywords: Parkinson’s disease, genetic mutations, pharmacology, protein misfolding, oxidative stress, dopamine, L-DOPA, purinergic receptors, P2X7R, PPAR, PGC-1α, α-synuclein, LRRK2, PARKIN, animal models, epidemiology, diagnosis, therapy, ubiquitin-proteasome system, imaging.