Coffee and Parkinson's disease

Abstract

Parkinson's disease (PD) is a prevalent neurodegenerative disease marked by dopaminergic neuronal loss and misfolded alpha-synuclein (α-syn) accumulation, which results in both motor and cognitive symptoms. Its occurrence grows with age, with a larger prevalence among males. Despite substantial study, effective medicines to reduce or stop the progression of diseases remain elusive. Interest has grown in examining dietary components, such as caffeine present in coffee, for potential medicinal effects. Epidemiological studies imply a lower incidence of PD with coffee drinking, attributable to caffeine's neuroprotective abilities. Beyond caffeine, coffee constituent like chlorogenic acid and cafestol have anti-Parkinsonian benefits. Moreover, coffee use has been related with variations in gut microbiota composition, which may reduce intestinal inflammation and prevent protein misfolding in enteric nerves, perhaps through the microbiota-gut-brain axis. This review gives a summary of the neuroprotective effects of coffee, investigating both its motor and non-motor advantages in individuals with PD as well as in experimental models of PD. We reviewed some bioactive constituents of coffee, their respective interactions with misfolded α-syn accumulation, and its emerging mechanisms associated to the gut microbiome.

Introduction

Parkinson's disease (PD) is the second most frequent neurologic disorder after Alzheimer's disease (Poewe et al., 2017), demonstrating an incidence that grows with age and a larger prevalence throughout the male population. The pathological characteristics of PD include the dopaminergic neurons' loss in a particular of the brain called the substantia nigra pars compacta. It is believed that in mentally sound individuals, around 3–5% of dopaminergic neuron (DA) are deteriorated every decade, but in PD patient, the rate of deterioration is greater than that found in a mentally healthy individual. Research autopsy samples of PD patients' brains indicated that about 70–75% of DA neurons are damaged at the time the disease becomes manifest (Dauer and Przedborski, 2003). This reveals that DA neurons have a high degree of functional flexibility, i.e., plasticity. In addition to the loss of these neurons, there is the development of neuronal proteinopathy inclusions dubbed Lewy bodies, made up of α-syn accumulation (Yasuda et al., 2013). Hence, PD has been related with a sort of dementia dubbed Lewy body dementia. Furthermore, according to a systematic analysis of Global Burden of Disease Study 2016, published in Lancet Neurology in 2018, PD becomes more common as people get older, with rates ranging from 41 to 100,000 in those in their 50s and up to 1900 per 100,000 in those aged 80 and above (Dorsey et al., 2018). This trend is similar to other age-related neurodegenerative diseases (NDDs) suggesting that the incidence of PD normally rises with age. Motor deficits including resting tremor, muscle rigidity, instability of posture, and bradykinesia are the primary signs of PD (Jankovic, 2008; Kouli et al., 2018), Additionally, non-motor symptoms are pre-clinically diagnosed before the commencement of the motor symptoms, these are sleep disorders, hallucinations, autonomic dysfunction, olfactory dysfunction, dementia, and depression (Greenland and Barker, 2018). Over the years, with the confirmation of α-syn aggregate as the significant cause of PD (Giráldez-Pérez et al., 2014), the largely distribution of α-syn aggregates in the brain is responsible for the listed PD's non-motor symptoms which have gained large recognition as vital parts of the disorder. In this review, for improved understanding of PD and gut in relation to the consumption of coffee and other caffeinated substances, the postulated etiology of PD needs to be known. There are two forms of PD in term of its etiology: First, in around 70% of situations, the aggregation of abnormal α-syn proteins have been seen to be created in the central nervous system (CNS). Second, for the other 30% of situations, this proteinopathies develop from the neurological system of the intestines—the Enteric nerve system (Schaffrath et al., 2023). A systematic review has discussed the interesting supposition that gut intestinal dysbiosis is the first step of a process that leads to PD due to alterations in gut microbiota and their metabolites that give rise to intestinal inflammation, which can also affect and change the gut-brain communication and the brain barrier, thereby contributing to inflammation of the brain and deterioration of its cells (Xiromerisiou et al., 2023). Importantly, despite the extensive research, there are currently no effective treatments available to slow down or stop the progression of this chronic neurodegenerative condition.

Given the lack of a treatment that can effectively alter the progression of PD, there is increasing interest in exploring various potential risk factors, such as dietary elements like caffeine, which could potentially modifies the development of the disease and provide therapeutic advantages. Over the years, the intake of coffee and foods that contain caffeine are speculated to be connected with reduced risk of PD (Hu et al., 2007; Palacios et al., 2012). A meta-analysis study conducted in both PD's patients and healthy persons revealed that consuming coffee or caffeinated foods can slow down the chances of having PD in healthy individuals. Additionally, it can also slow down the progression of PD in patients who already have it (Hong et al., 2020).

Coffee is the most frequently consumed caffeine-containing beverage which act as a psychostimulant (dePaula and Farah, 2019; Fredholm et al., 1999). Caffeine, one of the constituent of coffee is an alkaloid and naturally occurring, it is found in many plants. It has stimulatory, anti-inflammatory, antioxidative, and it helps managing pain, and it is part of the composition of many over-the-counter medications (Saraiva et al., 2023). This naturally derived bioactive compound which can be seen in some plant like Cola acuminata is the best-known ingredient in coffee and other beverages, such as energy drinks, soft drinks, and tea (Asuku et al., 2022; Jeszka-Skowron et al., 2021). After consumption, it is rapidly absorbed through the gastrointestinal tract to the blood and then to the liver, brain and kidney (Che et al., 2012). Additionally, drinking coffee regularly has several health benefits, including reducing the risk of heart and vascular disorders, improving the control of asthma, and lowering the risk of liver disease (O'Keefe et al., 2018). Some neurodegenerative disorders seem to be less severe in people who drink coffee regularly (Yenisetti, 2016). Caffeine is blocker of adenosine (A_2A) receptor. These receptors are popularly domiciled in the dopaminergic neurons. The activation of the adenosine A_2A receptors causes an increase in intracellular cAMP levels and glutamate extracellular release, resulting in neural excitotoxicity leading to neuronal cell death (Carpenter and Lebon, 2017). By antagonizing this receptor, caffeine reduced activity in the downstream phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling cascade, protecting neurons against hypercalcemia-induced damage and inflammation (Chen et al., 2001; Kolahdouzan and Hamadeh, 2017). By antagonizing the aforementioned pathways, caffeine increases motor activity and has an antidyskinetic effect via its effects on the dopaminergic system (Nicoletti et al., 2015) as well as enhancement of cognition in PD patient (Postuma et al., 2017). Furthermore, other constituents of coffee aside from caffeine have been shown to exert anti-parkinsonism symptoms. Coffee's constituents such as chlorogenic acid and cafestol have shown to be neuroprotective. Chlorogenic acid demonstrated anti-PD effects by alleviating the loss of dopamine neurons (Gao et al., 2023). On the other hand, cafestol, a well-known Nrf2-stimulator in coffee, gives a great neuroprotection in drosophila models of PD (Trinh et al., 2010). Studies have shown that coffee's consumption may slow down PD risk by altering gut microbiota composition, reducing intestinal inflammation and preventing protein misfolding in enteric nerves before getting to the CNS (Liu et al., 2022; Scheperjans et al., 2015a, Scheperjans et al., 2015b). Following the Gut-Brain Axis hypothesis propounded by Braak and colleagues in 2003 (Braak et al., 2003), further studies have been shown to corroborate the hypothesis by the α-syn's prion-like mechanism in allowing them to increase and propagate among brain cells in the nervous system and extend to large area from the gut and the brain via vagus nerves (Arotcarena et al., 2020; Hawkes et al., 2009). Therefore, if the beneficial impacts of consuming on PD are mediated through the microbiota-gut-brain axis' modulation, what responsibility might the microbes play in Braak's scenario?

This review summarized the neuroprotective roles of coffee looking into the motor and non-motor benefits of coffee and its constituents in patients that are associated with PD and other animal PD models. We described the potential constituents of coffee, how it interacts with the aggregation of α-syn and its novel emerging mechanisms associated with the gut microbiota.