Distinctive Evidence Involved in the Role of Endocannabinoid Signalling in Parkinson’s Disease: A Perspective on Associated Therapeutic Interventions

Abstract

Current pharmacotherapy of Parkinson’s disease (PD) is symptomatic and palliative, with levodopa/carbidopa therapy remaining the prime treatment, and nevertheless, being unable to modulate the progression of the neurodegeneration. No available treatment for PD can enhance the patient’s life-quality by regressing this diseased state. Various studies have encouraged the enrichment of treatment possibilities by discovering the association of the effects of the endocannabinoid system (ECS) in PD. These reviews delineate the reported evidence from the literature on the neuromodulatory role of the endocannabinoid system and expression of cannabinoid receptors in symptomatology, cause, and treatment of PD progression, wherein cannabinoid (CB) signalling experiences alterations of biphasic pattern during PD progression. Published papers to date were searched via MEDLINE, PubMed, etc., using specific key words in the topic of our manuscript. Endocannabinoids regulate the basal ganglia neuronal circuit pathways, synaptic plasticity, and motor functions via communication with dopaminergic, glutamatergic, and GABAergic signalling systems bidirectionally in PD. Further, gripping preclinical and clinical studies demonstrate the context regarding the cannabinoid compounds, which is supported by various evidence (neuroprotection, suppression of excitotoxicity, oxidative stress, glial activation, and additional benefits) provided by cannabinoid-like compounds (much research addresses the direct regulation of cannabinoids with dopamine transmission and other signalling pathways in PD). More data related to endocannabinoids efficacy, safety, and pharmacokinetic profiles need to be explored, providing better insights into their potential to ameliorate or even regress PD.

Multifaceted Role of Matrix Metalloproteinases in Neurodegenerative Diseases: Pathophysiological and Therapeutic Perspectives

“…With multifaceted etiologies and about two percent prevalence in the older populations (mainly >60 age), PD is one of the most common, long-term, age-related ND, which has been causing significant burden and disability in the quality of life [ 80 ]. It is proposed that the progression and pathogenesis of PD is associated with prominent characteristic i.e., α-synuclein inclusions in the Lewy bodies in affected areas of brain [ 81 ].…”

“…Thus, the validation of MMP blockers serve as a therapeutic opportunity, because BBB perturbations may also occur in neurodegeneration. Hence, MMPs and associated mechanisms may also be potential targets for neurodegenerative disorders [79] With multifaceted etiologies and about two percent prevalence in the older populations (mainly >60 age), PD is one of the most common, long-term, age-related ND, which has been causing significant burden and disability in the quality of life [80]. It is proposed that the progression and pathogenesis of PD is associated with prominent characteristic i.e., α-synuclein inclusions in the Lewy bodies in affected areas of brain [81].…”

Green Synthesis, Characterization, and Antibacterial Properties of Silver Nanoparticles Obtained by Using Diverse Varieties of Cannabis sativa Leaf Extracts

“…The main hemp phytochemicals that are synthesized in trichomes that cover the leaves, branches, and stems of the plant belong to the following classes: cannabinoids (more than 100), polyphenols, flavonoids, terpenoids (which give the smell of the crop), amides, amines, carbohydrates, fatty acids, and esters, with many of them having medical uses [ 8 ], alone or in diverse preparations. The results of several studies have demonstrated the involvement of phytocannabinoids in several central and peripheral pathophysiological mechanisms, namely: food intake (modulate hunger/satiety), multiple sclerosis, inflammation, pain [ 9 ], spasticity, colitis, nausea and vomiting, anorexia, Tourette syndrome, sleep disorders, anxiety, epilepsy, Alzheimer’s disease, and Parkinson’s disease [ 2 , 10 , 11 ]. Therefore, a strict pathway to obtain authorization for a potential medicinal product containing hemp preparations, which have little or no psychoactive effect because they contain low levels of Δ 9 -tetrahydrocannabinol (Δ 9 -THC), is required, and has been mentioned in a recent report from the European Monitoring Centre for Drugs and Drug Addiction [ 12 ].…”

The Endocannabinoid System: A Bridge between Alzheimer’s Disease and Gut Microbiota

“…This unique function of eCBs suggested their investigation as therapeutic targets for human diseases affecting central nervous system (CNS) [13]. Indeed, the eCB system dysregulation in the CNS has been increasingly implicated in the physiopathology of neurodegenerative and neuropsychiatric disorders, such as AD [18], Parkinson's disease [34], Huntington's disease [35], multiple sclerosis [36] schizophrenia [37] and anxiety disorders [38]. CB 1 and CB 2 are differently expressed throughout human body and their distribution correlated with their specific physiological roles.…”