Potential Role of Caffeine in the Treatment of Parkinson’s Disease

Abstract

Parkinson’s disease [PD] is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting 1% of the population over the age of 55. The underlying neuropathology seen in PD is characterised by progressive loss of dopaminergic neurons in the substantia nigra pars compacta with the presence of Lewy bodies. The Lewy bodies are composed of aggregates of α-synuclein. The motor manifestations of PD include a resting tremor, bradykinesia, and muscle rigidity. Currently there is no cure for PD and motor symptoms are treated with a number of drugs including levodopa [L-dopa]. These drugs do not delay progression of the disease and often provide only temporary relief. Their use is often accompanied by severe adverse effects. Emerging evidence from both in vivo and in vitro studies suggests that caffeine may reduce parkinsonian motor symptoms by antagonising the adenosine A2A receptor, which is predominately expressed in the basal ganglia. It is hypothesised that caffeine may increase the excitatory activity in local areas by inhibiting the astrocytic inflammatory processes but evidence remains inconclusive. In addition, the co-administration of caffeine with currently available PD drugs helps to reduce drug tolerance, suggesting that caffeine may be used as an adjuvant in treating PD. In conclusion, caffeine may have a wide range of therapeutic effects which are yet to be explored, and therefore warrants further investigation in randomized clinical trials.

Acute doses of caffeine shift nervous system cell expression profiles toward promotion of neuronal projection growth

“…Although the results were due to acute effects of caffeine treatment, it would be interesting to see if these pathways are also up-regulated with prolonged exposure to caffeine. If the activation of neuronal connection/development pathways could be observed in a long term treatment model, it might help explain the links between caffeine and improved cognitive performance, as well as suggested protective effects against Alzheimer disease in epidemiological studies 41 – 43 .…”

Caffeine Protects Dopaminergic Neurons From Dopamine-Induced Neurodegeneration via Synergistic Adenosine-Dopamine D2-Like Receptor Interactions in Transgenic Caenorhabditis elegans

“…Further, the pathological rotational behavior in rats was also suggestive of possible depletion of brain dopamine, which parallels to neurodegeneration (Willis and Sandyk, 1993 ). However, given that caffeine was shown to protect neurons (Kolahdouzan and Hamadeh, 2017 ), enhance cognition and physical performance (Cappelletti et al, 2015 ), and that caffeine can reduce aberrant motor symptoms found commonly in parkinsonism (Roshan et al, 2016 ), a more profound mechanism must be present. To this end, suggestions were made that it is in fact the antagonism of A1 A R s that enhances locomotion and provides for central nervous stimulation (by antagonizing the suppressive A1 A R s), and that it is the antagonism of A2A A R s that lead to dopamine receptor sensitization and therefore aggravation of dopamine-related symptoms (Hadfield and Milio, 1989 ; Popoli et al, 1996 ; Górska and Golembiowska, 2015 ).…”

Lentiviral Vector-Mediated SHC3 Silencing Exacerbates Oxidative Stress Injury in Nigral Dopamine Neurons by Regulating the PI3K-AKT-FoxO Signaling Pathway in Rats with Parkinson’s Disease

“…Parkinson's disease (PD), as the second most prevalent degenerative disorder of the central nervous system, currently affects more than 100, 000 individuals worldwide [22][23][24]. Despite extensive preclinical studies in PD animal models, there is still a lack of effective neuroprotective drugs for PD available [25,26].…”