Potential of Antibiotics for the Treatment and Management of Parkinson's Disease: An Overview

Abstract

: Evidences have emerged over the last 2 decades to ascertain the proof of concepts viz. mitochondrial dysfunction, inflammation-derived oxidative damage and cytokine-induced toxicity that play a significant role in Parkinson's disease (PD). The available pharmacotherapies for PD are mainly symptomatic and typically indications of L-DOPA to restrain dopamine deficiency and their consequences. In the 21st century, the role of the antibiotics has emerged at the forefront of medicine in health and human illness. There are several experimental and pre-clinical evidences that supported the potential use of antibiotic as neuroprotective agent. The astonishing effects of antibiotics and their neuroprotective properties against neurodegeneration and neuro-inflammation would be phenomenal for the development of effective therapy against PD. Antibiotics are also testified as useful not only to prevent the formation of alpha-synuclein but also act on mitochondrial dysfunction and neuro-inflammation. Thus, the possible therapy with antibiotics in PD would impact both the pathways leading to neuronal cell death in substantia nigra and pars compacta in midbrain. Moreover, the antibiotic based pharmacotherapy will open a scientific research passageway to add more to the evidence based and rational use of antibiotics for the treatment and management of PD and other neurodegenerative disorders.

Effects of levodopa on gut bacterial antibiotic resistance in Parkinson’s disease rat

“…To conclude, this study revealed that levodopa therapy in PD rat model led to changes in resistance genes, which might be related to alterations in intestinal flora. Antibiotics have emerged as potential drugs to treat PD, but they still face great challenges, such as bacterial resistance ( Yadav et al, 2021 ). Levodopa remains the drug of first choice for PD, although it generates several side effects ( Lane, 2019 ; Cilia et al, 2020 ).…”

“…Numerous experimental and pre-clinical studies have shown that antibiotics may be used as neuroprotective drugs. Additionally, evidence suggests that antibiotics are helpful in reducing neuro-inflammation and mitochondrial dysfunction in addition to avoiding the production of α-synuclein ( Yadav et al, 2021 ). In PD animal models, tetracyclines conferred DA neuroprotection via its anti-inflammatory, anti-oxidant and anti-apoptotic activities, doxycycline can reduce the production of mitochondrial-derived reactive oxygen species and prevent the aggregation and seeding of recombinant α-synuclein, rats exposed to rotenone-induced motor deficits can be improved by minocycline, which increased TH expression and inhibited the release of ROS and NO in the SN ( Sun et al, 2019 ; Dominguez-Meijide et al, 2021 ; Rahmani et al, 2022 ).…”

Cognitive- and memory-enhancing effects of Augmentin in Alzheimer’s rats through regulation of gene expression and neuronal cell apoptosis

“…Previous research confirmed the role of Augmentin components (amoxicillin and clavulanic acid) in neurological disorders. In addition, recent research has demonstrated the potential of antibiotic-based therapy for treating and managing Parkinson’s disease and other neurodegenerative disorders ( Yadav et al, 2021 ). In the case of amoxicillin, its administration has been reported to reduce epileptic seizures in patients with epilepsy and to reduce discrete body twitches ( Raposo et al, 2016 ).…”

The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment

“…Although they are mainly used to counteract or prevent bacterial infections, their additional anti-inflammatory, immunomodulator, neuroprotective, antiamyloidogenic and antioxidant properties are becoming of increasing interest in the context of neurological disorders, including neurodegeneration [ 205 , 206 , 207 , 208 , 209 ]. Indeed, beside counteracting dysbiosis and constipation [ 210 ], it has been demonstrated that certain antibiotics can inhibit the activity of matrix metalloproteinases and prevent mitochondria dysfunction, microglia activation, protein misfolding and α-synuclein aggregation [ 211 , 212 , 213 , 214 , 215 ]. For example, treating mice where PD has been induced by MPTP with a cocktail of broad-spectrum antibiotics (ampicillin, metronidazole, and neomycin sulfate) was found to preserve TH and dopamine transporter immunoreactivities, which are generally lost upon MPTP administration [ 216 ].…”