Non-pharmacological therapy has gained popularity in the intervention of Alzheimer\'s disease (AD) due to its apparent therapeutic effectiveness and the limitation of biological drug. A wealth of research indicates that music interventions can enhance cognition, mood and behavior in individuals with AD. Nonetheless, the underlying mechanisms behind these improvements have yet to be fully and systematically delineated. This review aims to holistically review how music-based intervention (MBI) ameliorates abnormal emotion, cognition decline, and behavioral changes in AD patients. We cover several key dimensions: the regulation of MBIs on cerebral blood flow (CBF), their impact on neurotransmission (including GABAergic and monoaminergic transmissions), modulation of synaptic plasticity, and hormonal release. Additionally, we summarize the clinical applications and limitations of active music-based intervention (AMBI), passive music-based intervention (PMBI), and hybrid music-based intervention (HMBI). This thorough analysis enhances our understanding of the role of MBI in AD and supports the development of non-pharmacological therapeutic strategies.

This literature review explores the pivotal roles of the Uncoordinated-13 (UNC13) protein family, encompassing UNC13A, UNC13B, UNC13C, and UNC13D, in the pathogenesis of various human diseases. These proteins, which are evolutionarily conserved and crucial for synaptic vesicle priming and exocytosis, have been implicated in a range of disorders, spanning from neurodegenerative diseases like amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) to immune-related conditions such as familial hemophagocytic lymphohistiocytosis (FHL). The involvement of UNC13A in neurotransmitter release and synaptic plasticity is linked to ALS and FTD, with genetic variations affecting disease progression. UNC13B, which is closely related to UNC13A, plays a role in autism spectrum disorders (ASD), epilepsy, and schizophrenia. UNC13C is implicated in oral squamous cell carcinoma (OSCC) and hepatocellular carcinoma (HCC), and has a neuroprotective role in Alzheimer\'s disease (AD). UNC13D has an essential role in immune cell function, making it a key player in FHL. This review highlights the distinct molecular functions of each UNC13 family member and their implications in disease contexts, shedding light on potential therapeutic strategies and avenues for future research. Understanding these proteins\' roles offers new insights into the management and treatment of neurological and immunological disorders.

Nearly 5 decades ago, the effect of trigeminal nerve stimulation (TNS) on cerebral blood flow was observed for the first time. This implication directly led to further investigations and TNS\' success as a therapeutic intervention. Possessing unique connections with key brain and brainstem regions, TNS has been observed to modulate cerebral vasodilation, brain metabolism, cerebral autoregulation, cerebral and systemic inflammation, and the autonomic nervous system. The unique range of effects make it a prime therapeutic modality and have led to its clinical usage in chronic conditions such as migraine, prolonged disorders of consciousness, and depression. This review aims to present a comprehensive overview of TNS research and its broader therapeutic potentialities. For the purpose of this review, PubMed and Google Scholar were searched from inception to August 28, 2023 to identify a total of 89 relevant studies, both clinical and pre-clinical. TNS harnesses the release of vasoactive neuropeptides, modulation of neurotransmission, and direct action upon the autonomic nervous system to generate a suite of powerful multitarget therapeutic effects. While TNS has been applied clinically to chronic pathological conditions, these powerful effects have recently shown great potential in a number of acute/traumatic pathologies. However, there are still key mechanistic and methodologic knowledge gaps to be solved to make TNS a viable therapeutic option in wider clinical settings. These include bimodal or paradoxical effects and mechanisms, questions regarding its safety in acute/traumatic conditions, the development of more selective stimulation methods to avoid potential maladaptive effects, and its connection to the diving reflex, a trigeminally-mediated protective endogenous reflex. The address of these questions could overcome the current limitations and allow TNS to be applied therapeutically to an innumerable number of pathologies, such that it now stands at the precipice of becoming a ground-breaking therapeutic modality.

Epilepsy is a common neurological disorder associated with alterations of excitation-inhibition balance within brain neuronal networks. GABAA receptor neurotransmission is the most prevalent form of inhibitory neurotransmission and is strongly implicated in both the pathophysiology and treatment of epilepsy, serving as a primary target for antiseizure medications for over a century. It is now established that GABA exerts a multifaceted influence through an array of GABAA receptor subtypes that extends far beyond simply negating excitatory activity. As the role of GABAA neurotransmission within inhibitory circuits is elaborated, this will enable the development of precision therapies that correct the network dysfunction underlying epileptic pathology.

Synaptic dysregulations often result in damaging effects on the central nervous system, resulting in a wide range of brain and neurodevelopment disorders that are caused by mutations disrupting synaptic proteins. SYT1, an identified synaptotagmin protein, plays an essential role in mediating the release of calcium-triggered neurotransmitters (NT) involved in regular synaptic vesicle exocytosis. Considering the significant role of SYT1 in the physiology of synaptic neurotransmission, dysfunction and degeneration of this protein can result in a severe neurological impairment. Genetic variants lead to a newly discovered rare disorder, known as SYT1-associated neurodevelopment disorder. In this review, we will discuss in depth the function of SYT1 in synapse and the underlying molecular mechanisms. We will highlight the genetic basis of SYT1-associated neurodevelopmental disorder along with known phenotypes, with possible interventions and direction of research.

Migraine is a neurological disorder defined by episodic attacks of chronic pain associated with nausea, photophobia, and phonophobia. It is known to be a complex disease with several environmental and genetic factors contributing to its susceptibility. Risk factors for migraine include head or neck injury (Arnold, Cephalalgia 38(1):1-211, 2018). Stress and high temperature are known to trigger migraine, while sleep disorders and anxiety are considered to be the comorbid conditions with migraine. Studies have reported various biomarkers, including genetic variants, proteins, and metabolites implicated in migraine\'s pathophysiology. Using the \"omics\" approach, which deals with genetics, transcriptomics, proteomics, and metabolomics, more specific biomarkers for various migraine can be identified. On account of its multifactorial nature, migraine is an ideal study model focusing on integrated omics approaches, including genomics, transcriptomics, proteomics, and metabolomics. The current review has been compiled with an aim to focus on the genomic alterations especially involved in the regulation of glutamatergic neurotransmission, cortical excitability, ion channels, solute carrier proteins, or receptors; their expression in migraine patients and also specific proteins and metabolites, including some inflammatory biomarkers that might represent the migraine phenotype at the molecular level. The systems biology approach holds the promise to understand the pathophysiology of the disease at length and also to identify the specific therapeutic targets for novel interventions.

Parkinson\'s Disease (PD) is a disease that involves neurodegeneration and is characterised by the motor symptoms which include muscle rigidity, tremor, and bradykinesia. Other non-motor symptoms include pain, depression, anxiety, and psychosis. This disease affects up to ten million people worldwide. The pathophysiology behind PD is due to the neurodegeneration of the nigrostriatal pathway. There are many conventional drugs used in the treatment of PD. However, there are limitations associated with conventional drugs. For instance, levodopa is associated with the on-off phenomenon, and it may induce wearing off as time progresses. Therefore, this review aimed to analyze the newly approved drugs by the United States-Food and Drug Administration (US-FDA) from 2016-2019 as the adjuvant therapy for the treatment of PD symptoms in terms of efficacy and safety. The new drugs include safinamide, istradefylline and pimavanserin. From this review, safinamide is considered to be more efficacious and safer as the adjunct therapy to levodopa as compared to istradefylline in controlling the motor symptoms. In Study 016, both safinamide 50 mg (p = 0.0138) and 100 mg (p = 0.0006) have improved the Unified Parkinson\'s Disease Rating Scale (UPDRS) part III score as compared to placebo. Improvement in Clinical Global Impression-Change (CGI-C), Clinical Global Impression-Severity of Illness (CGI-S) and off time were also seen in both groups of patients following the morning levodopa dose. Pimavanserin also showed favorable effects in ameliorating the symptoms of Parkinson\'s Disease Psychosis (PDP). A combination of conventional therapy and non-pharmacological treatment is warranted to enhance the well-being of PD patients.

BACKGROUND: Vortioxetine is a multimodal-acting antidepressant that provides improvements on cognitive function aside from antidepressants and anxiolytic effects. Vortioxetine has been found to be one of the most effective and best tolerated options for major depressive disorder (MDD) in head-to-head trials.
METHODS: The present review intends to gather the most relevant and pragmatic data of vortioxetine in MDD, specially focusing on new studies that emerged between 2015 and 2020.
CONCLUSIONS: Vortioxetine is the first antidepressant that has shown improvements both in depression and cognitive symptoms, due to the unique multimodal mechanism of action that combine the 5-HT reuptake inhibition with modulations of other key pre- and post-synaptic 5-HT receptors (agonism of 5-HT1A receptor, partial agonism of 5-HT1B receptor, and antagonism of 5-HT3, 5-HT1D and 5-HT7 receptors). This new mechanism of action can explain the dose-dependent effect and can be responsible for its effects on cognitive functioning and improved tolerability profile. Potential analgesic and anti-inflammatory properties observed in preclinical studies as well as interesting efficacy and tolerability results of clinical studies with specific target groups render it a promising therapeutic option for patients with MDD and concomitant conditions (as menopause symptoms, pain, inflammation, apathy, sleep and/or metabolic abnormalities).

Levodopa remains the primary drug for controlling motor symptoms in Parkinson\'s disease through the whole course, but over time, complications develop in the form of dyskinesias, which gradually become more frequent and severe. These abnormal, involuntary, hyperkinetic movements are mainly characteristic of the ON phase and are triggered by excess exogenous levodopa. They may also occur during the OFF phase, or in both phases. Over the past 10 years, the issue of levodopa-induced dyskinesia has been the subject of research into both the substrate of this pathology and potential remedial strategies. The purpose of the present study was to review the results of recent research on the background and treatment of dyskinesia. To this end, databases were reviewed using a search strategy that included both relevant keywords related to the topic and appropriate filters to limit results to English language literature published since 2010. Based on the selected papers, the current state of knowledge on the morphological, functional, genetic and clinical features of levodopa-induced dyskinesia, as well as pharmacological, genetic treatment and other therapies such as deep brain stimulation, are described.

OBJECTIVE: The aim of the work is to point out the transmission of electrical voltage changes in the visual analyser and thus the efficiency of the bionic eye.
METHODS: The review deals with the question of the transmission of electrical changes in visual path voltage under physiological and pathological conditions. In particular, it points to feedback autoregulatory damage not only of primarily altered cellular structures, but of all other, both horizontally and vertically localized. Based on the results of functional magnetic resonance imaging and electrophysiological methods, it shows the pathology of the entire visual pathway in three eye diseases: retinitis pigmentosa, age-related macular degeneration and glaucoma.
RESULTS: The thesis also provides an overview of possible systems that are used to replace lost vision, from epiretinal, subretinal, suprachoroidal implants, through stimulation of the optic nerve, corpus geniculatum laterale to the visual cortex.
CONCLUSIONS: Due to the pathology of neurotransmission, bionic eye systems cannot be expected to be restored after stabilization of binocular functions.