Metformin, a widely prescribed medication for type 2 diabetes, has garnered increasing attention for its potential neuroprotective properties due to the growing demand for treatments for Alzheimer’s, Parkinson’s, and motor neuron diseases. This review synthesizes experimental and clinical studies on metformin’s mechanisms of action and potential therapeutic benefits for neurodegenerative disorders. A comprehensive search of electronic databases, including PubMed, MEDLINE, Embase, and Cochrane library, focused on key phrases such as “metformin”, “neuroprotection”, and “neurodegenerative diseases”, with data up to September 2023. Recent research on metformin’s glucoregulatory mechanisms reveals new molecular targets, including the activation of the LKB1–AMPK signaling pathway, which is crucial for chronic administration of metformin. The pleiotropic impact may involve other stress kinases that are acutely activated. The precise role of respiratory chain complexes (I and IV), of the mitochondrial targets, or of the lysosomes in metformin effects remains to be established by further research. Research on extrahepatic targets like the gut and microbiota, as well as its antioxidant and immunomodulatory properties, is crucial for understanding neurodegenerative disorders. Experimental data on animal models shows promising results, but clinical studies are inconclusive. Understanding the molecular targets and mechanisms of its effects could help design clinical trials to explore and, hopefully, prove its therapeutic effects in neurodegenerative conditions.

Background: Non-motor symptoms in Parkinson’s disease (PD) consist of a wide spectrum of gastrointestinal impairment, urinary dysfunction, sleep disturbances, fatigue and psychiatric disorders. Mood disorders like anxiety and depression are linked to general well-being and overall quality of life, therefore influencing the amount and quality of restful sleep that the patients can achieve. Objectives: The aim of this study is to determine the prevalence and characteristics of anxiety and depression in PD and to identify the factors that correlate with sleep disturbances. Methods: We conducted a case–control study which included 131 PD patients and 131 controls. Descriptive data was collected, and validated scales and questionnaires regarding sleep, motor symptoms and symptoms related to anxiety and depression were administered. Patients were divided into groups by the presence or absence of sleep disorders (“bad sleepers” and “good sleepers”) and by the presence or absence of anxiety and depression. Comparative analysis was performed. Results: PD patients reported more clinically significant depression than controls and those with concomitant sleep impairment scored higher on depression- and anxiety-specific scales than their better-sleeping counterparts. Age, motor status and sleep impairment were found to be factors associated with depression in PD patients. The presence of sleep disorders was also associated with anxiety. Conclusions: Depression and anxiety are frequent in PD and are associated with comorbid sleep disturbances.