Parkinson disease

Abstract

Parkinson disease (PD) is the most common neurodegenerative movement disorder. In Europe, prevalence and incidence rates for PD are estimated at approximately 108–257/100 000 and 11–19/100 000 per year, respectively. Risk factors include age, male gender and some environmental factors. The aetiology of the disease in most patients is unknown, but different genetic causes have been identified. Although familial forms of PD account for only 5%–15% of cases, studies on these families provided interesting insight on the genetics and the pathogenesis of the disease allowing the identification of genes implicated in its pathogenesis and offering critical insights into the mechanisms of disease. The cardinal motor symptoms of PD are tremor, rigidity, bradykinesia/akinesia and postural instability, but the clinical picture includes other motor and non‐motor symptoms. Its diagnosis is principally clinical, although specific investigations can help the differential diagnosis from other forms of parkinsonism. Pathologically, PD is characterized by the loss of dopaminergic neurons in the pars compacta of the substantia nigra and by accumulation of misfolded α‐synuclein, which is found in intra‐cytoplasmic inclusions called Lewy bodies. Currently available treatments offer good control of motor symptoms but do not modify the evolution of the disease. This article is intended to provide a comprehensive, general and practical review of PD for the general neurologist.

Defining the Neural Kinome: Strategies and Opportunities for Small Molecule Drug Discovery to Target Neurodegenerative Diseases

“…Other FDA approved treatments for PD are predominantly focused on increasing or substituting for low levels of DA to manage tremors and irregular movements: DA agonists directly stimulate the DA receptors, monoamine oxidase B inhibitors prolong DA stimulation by decreasing DA breakdown, and catechol-O-methyl transferase inhibitors delay the breakdown of L-DOPA. 10 Non-dopaminergic treatments include anticholinergics, adenosine 2A antagonists, and a drug that is reported to act via multiple mechanisms to exert anti-Parkinsonian effects (amantadine). 20 These FDA-approved drugs can be used as alternatives to L-DOPA, in addition to L-DOPA, or in combination with one another.…”

“…been thought to be mainly composed of alpha-synuclein and ubiquitin. 10 A recent study, however, demonstrated that Lewy bodies are composed of a membranous medley rather than protein fibrils, which includes membrane fragments, lipids, and other cellular material. 11 More recently, studying immune dysregulation in PD has attracted increased interest as activated microglia and T cells have been found in the SN of PD patients.…”

“…12 Aside from the motor symptoms of PD, patients exhibit non-motor features years before clinical diagnosis, including a loss of smell, depression, anxiety, constipation, and the biggest predictor of PD in prodromal patients, rapid eye movement (REM) sleep behavior disorder (RBD). 10 RBD is characterized by loss of REM sleep paralysis, allowing patients to "act out" dreams and represents the highest predictive value for PD, giving clinicians the ability to intervene early in the course of the disease before neuronal loss progresses past rescue and before symptomatic therapies confound assessments. 13 ALS is the most common motor neuron (MN) disorder and the third most common adult-onset neurodegenerative disease after AD and PD.…”

Application of Iron Oxide Nanoparticles in the Diagnosis and Treatment of Neurodegenerative Diseases With Emphasis on Alzheimer’s Disease

“…Parkinson's disease (PD) is the second most common neurodegenerative disease in the whole world (Balestrino and Schapira, 2019). PD mainly affects the locomotor system by degenerating the neuron, finally leading to severe disability (Balestrino and Schapira, 2019). The clinical criteria for diagnosis of PD depend mainly on the observation of movement disorders such as cogwheel rigidity, bradykinesia, resting tremor, etc.…”

“…The clinical criteria for diagnosis of PD depend mainly on the observation of movement disorders such as cogwheel rigidity, bradykinesia, resting tremor, etc. (Balestrino and Schapira, 2019). In the dopaminergic neurons, phosphor-α-synuclein molecules can aggregate with one another easily to form Lewy body, and these degenerative dopaminergic neurons lose the function of expressing dopamine, finally leading to the damage of the motor cortex and movement disorders (Ikenaka et al, 2019).…”