Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease after Alzheimer’s disease, globally. Dopaminergic neuron degeneration in substantia nigra pars compacta and aggregation of misfolded alpha-synuclein are the PD hallmarks, accompanied by motor and non-motor symptoms. Several viruses have been linked to the appearance of a post-infection parkinsonian phenotype. Coronavirus disease 2019 (COVID-19), caused by emerging severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, has evolved from a novel pneumonia to a multifaceted syndrome with multiple clinical manifestations, among which neurological sequalae appear insidious and potentially long-lasting. Exosomes are extracellular nanovesicles bearing a complex cargo of active biomolecules and playing crucial roles in intercellular communication under pathophysiological conditions. Exosomes constitute a reliable route for misfolded protein transmission, contributing to PD pathogenesis and diagnosis. Herein, we summarize recent evidence suggesting that SARS-CoV-2 infection shares numerous clinical manifestations and inflammatory and molecular pathways with PD. We carry on hypothesizing that these similarities may be reflected in exosomal cargo modulated by the virus in correlation with disease severity. Travelling from the periphery to the brain, SARS-CoV-2-related exosomal cargo contains SARS-CoV-2 RNA, viral proteins, inflammatory mediators, and modified host proteins that could operate as promoters of neurodegenerative and neuroinflammatory cascades, potentially leading to a future parkinsonism and PD development.

Parkinson’s disease is a progressive neurodegenerative disorder with motor, physical and behavioral symptoms that can have a profound impact on the patient’s quality of life. Most cases are idiopathic, and the exact mechanism of the disease’s cause is unknown. The current hypothesis focuses on the gut-brain axis and states that gut microbiota dysbiosis can trigger inflammation and advances the development of Parkinson’s disease. This systematic review presents the current knowledge of gut microbiota analysis and inflammation based on selected studies on Parkinson’s patients and experimental animal models. Changes in gut microbiota correlate with Parkinson’s disease, but only a few studies have considered inflammatory modulators as important triggers of the disease. Nevertheless, it is evident that proinflammatory cytokines and chemokines are induced in the gut, the circulation, and the brain before the development of the disease’s neurological symptoms and exacerbate the disease. Increased levels of tumor necrosis factor, interleukin-1β, interleukin-6, interleukin-17A and interferon-γ can correlate with altered gut microbiota. Instead, treatment of gut dysbiosis is accompanied by reduced levels of inflammatory mediators in specific tissues, such as the colon, brain and serum and/or cerebrospinal fluid. Deciphering the role of the immune responses and the mechanisms of the PD-associated gut microbiota will assist the interpretation of the pathogenesis of Parkinson’s and will elucidate appropriate therapeutic strategies.

We sought to assess the efficacy of combining onabotulinumtoxinA (BoNTA) as add-on therapy to carbamazepine or oxcarbazepine in treatment-refractory patients with trigeminal neuralgia (TGN) who failed to respond (less than 30% response rate) to adequate monotherapy. We conducted a retrospective study on 15 patients with a definite diagnosis of TGN, according to the established criteria, and underwent BoNTA as part of their treatment plan. A single BoNTA session was administered subcutaneously, according to patients’ perceived zone of pain, at different dosages ranging from 30 to 200 units (mean ± standard deviation: 87.3 ± 39.2). All patients (15/15; 100%) reported large reductions in the severity of their TGN-related neuropathic pain. The mean pain score on the VAS scale significantly decreased from 9.3 ± 1.1 to 3.7 ± 1.2 at 2 weeks after injecting BoNTA (p < 0.001) and remained stable at 4 and 24 weeks post-injection. Regarding the impact of BoNTA on patients’ health-related quality of life, there were significant improvements in both the physical and mental health domains (p < 0.05) of SF-36 tool. BoNTA may be a safe and effective treatment option for patients with refractory TGN when added on to carbamazepine or oxcarbazepine. The use of a single BoNTA session for TGN treatment may be an alternative to surgical interventions and as add-on treatment to oral medications, providing patients with a minimally invasive, effective, safe and well-tolerated option.

The purpose of our study was to obtain evidence that an unsupervised tele-exercise program (TE_group) via an online platform is a feasible alternative to a hybrid mode of supervised and unsupervised exercise (HE_group) sessions for improving fitness indexes, respiratory and cognitive functions, and biomarkers of oxidative stress in patients recovering from COVID-19. Forty-nine patients with long post-COVID-19 were randomly divided into two groups (HE_group: n = 24, age 60.0 ± 9.5 years versus TE_group: n = 25, age 58.7 ± 9.5 years). For each patient, we collected data from body composition, oxidative stress, pulmonary function, physical fitness, and cognitive function before and after the 12-week exercise rehabilitation program (ERP). Our data showed differences in both groups before and after 12-week ERP on fitness indicators, body composition, and pulmonary function indicators. Our findings demonstrated differences between groups after 12-week ERP on adjustment in the domains of cognitive function (HE_group increased the “visuospatial” domain: 3.2 ± 1.1 versus 3.5 ± 0.8 score, p = 0.008 and TE_group increased the “memory” domain: 3.3 ± 1.0 versus 3.8 ± 0.5 score, p = 0.003; after 12-week ERP showed differences between groups in domain “attention” TE_group: 4.8 ± 1.5 versus HE_group: 3.6 ± 1.8 score, p = 0.014) and the diffusing capacity for carbon monoxide (HE_group increased the percent of predicted values at 0.5 ± 32.3% and TE_group at 26.0 ± 33.1%, p < 0.001). These findings may be attributed to the different ways of learning exercise programs, resulting in the recruitment of different neural circuits.

Background: Type I interferon signalling dysregulation is a hallmark of SARS‐CoV‐2 infection and among significantly perturbed pathways in Alzheimer’s disease. In a previous study, we predicted the involvement of this pathway in the development of SARS‐CoV‐2 Associated Neurocognitive Disorder (SAND) via a crosstalk between peripheral immunity and the CNS. The purpose of this study is to determine whether current data support provide external validation to our pathogenetic hypothesis.Method: Data for our validation analyses were leveraged from studies of frontal cortex (FC) transcriptomes donated by Alzheimer’s disease and COVID‐19 patients vs. controls, respectively. An additional dataset of nasal epithelial cells from COVID‐19 patients was also used as a putative crosstalk site. Enrichment analyses were employed to provide an unbiased estimate of the enrichment of Type I interferon responses. Furthermore, we performed a literature search in order to identify studies on the effects of COVID‐19 on two different settings: (a) to determine the effects of peripheral exosome cargo on CNS tissue (b) to determine the cargo of neuronal‐derived exosomes. For enrichment analyses, a false discover rate (FDR) <0.05 was considered statistically significant.Result: The type I interferon pathway (IFN‐I; GO:0060337) was significantly enriched in both Alzheimer’s disease and COVID‐19 FC transcriptomes, as well as nasal epithelia of COVID‐19 patients. Common genes in both IFN‐I FC signatures included PSMB8, IP6K2, IFI35, EGR1, ISG20, MYD88, IFITM1, SP100, GBP2, IFITM3, OASL, IRF1, IRF2, MX2, IFNA2, IRF9, IFIT3, STAT2, HLA‐C, SAMHD1, IFI27, IFITM2, IRF7, BST2. At least one study reports on miR‐148a and miR‐590 as exosomal cargo of infected non‐neuronal cells capable of affecting IFN‐I responses and inducing microglial activation, supporting the role of exosomes as facilitators of IFN‐I crosstalk between the periphery and the CNS. Correspondingly, at least one study reports on proteopathic seeds as cargo of neuron‐derived exosomes.Conclusion: Independent studies and data support continue to corroborate our hypothesis that type I interferon pathway dysregulation as a result of peripheral – CNS immune crosstalk may mediate neuroinflammation and Alzheimer’s disease‐like pathology as observed in SAND.