Neurotransmitters are molecules that amplify, transmit, and convert signals in cells, having an essential role in information transmission throughout the nervous system. Hundreds of such chemicals have been discovered in the last century, continuing to be identified and studied concerning their action on brain health. These substances have been observed to influence numerous functions, including emotions, thoughts, memories, learning, and movements. Thus, disturbances in neurotransmitters’ homeostasis started being correlated with a plethora of neurological and neurodegenerative disorders. In this respect, the present paper aims to describe the most important neurotransmitters, broadly classified into canonical (e.g., amino acids, monoamines, acetylcholine, purines, soluble gases, neuropeptides) and noncanonical neurotransmitters (e.g., exosomes, steroids, D-aspartic acid), and explain their link with some of the most relevant neurological conditions. Moreover, a brief overview of the recently developed neurotransmitters’ detection methods is offered, followed by several considerations on the modulation of these substances towards restoring homeostasis.

https://www.mdpi.com/1422-0067/23/11/5954/pdf?version=1653553978

Neurotransmitters—Key Factors in Neurological and Neurodegenerative Disorders of the Central Nervous System

Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder in which patients present inattention, hyperactivity, and impulsivity. The etiology of this condition is diverse, including environmental factors and the presence of variants of some genes. However, a great diversity exists among patients regarding the presence of these ADHD-associated factors. Moreover, there are variations in the reported neurophysiological correlates of ADHD. ADHD is often treated pharmacologically, producing an improvement in symptomatology, albeit there are patients who are refractory to the main pharmacological treatments or present side effects to these drugs, highlighting the importance of developing other therapeutic options. Different non-pharmacological treatments are in this review addressed, finding diverse results regarding efficacy. Altogether, ADHD is associated with different etiologies, all of them producing changes in brain development, leading to the characteristic symptomatology of this condition. Given the heterogeneous etiology of ADHD, discussion is presented about the convenience of personalizing ADHD treatment, whether pharmacological or non-pharmacological, to reach an optimum effect in the majority of patients. Approaches to personalizing both pharmacological therapy and neurofeedback are presented.

https://www.mdpi.com/2075-4426/11/3/166/pdf

ADHD: Reviewing the Causes and Evaluating Solutions.

RNA modifications are dynamic and reversible chemical modifications on substrate RNA that are regulated by specific modifying enzymes. They play important roles in the regulation of many biological processes in various diseases, such as the development of cancer and other diseases. With the help of advanced sequencing technologies, the role of RNA modifications has caught increasing attention in human diseases in scientific research. In this review, we briefly summarized the basic mechanisms of several common RNA modifications, including m6A, m5C, m1A, m7G, Ψ, A-to-I editing and ac4C. Importantly, we discussed their potential functions in human diseases, including cancer, neurological disorders, cardiovascular diseases, metabolic diseases, genetic and developmental diseases, as well as immune disorders. Through the "writing-erasing-reading" mechanisms, RNA modifications regulate the stability, translation, and localization of pivotal disease-related mRNAs to manipulate disease development. Moreover, we also highlighted in this review all currently available RNA-modifier-targeting small molecular inhibitors or activators, most of which are designed against m6A-related enzymes, such as METTL3, FTO and ALKBH5. This review provides clues for potential clinical therapy as well as future study directions in the RNA modification field. More in-depth studies on RNA modifications, their roles in human diseases and further development of their inhibitors or activators are needed for a thorough understanding of epitranscriptomics as well as diagnosis, treatment, and prognosis of human diseases. 

RNA modification: mechanisms and therapeutic targets

In recent years, N7-methylguanosine (m7G) methylation, originally considered as messenger RNA (mRNA) 5' caps modifications, has been identified at defined internal positions within multiple types of RNAs, including transfer RNAs, ribosomal RNAs, miRNA, and mRNAs. Scientists have put substantial efforts to discover m7G methyltransferases and methylated sites in RNAs to unveil the essential roles of m7G modifications in the regulation of gene expression and determine the association of m7G dysregulation in various diseases, including neurological disorders. Here, we review recent findings regarding the distribution, abundance, biogenesis, modifiers, and functions of m7G modifications. We also provide an up-to-date summary of m7G detection and profile mapping techniques, databases for validated and predicted m7G RNA sites, and web servers for m7G methylation prediction. Furthermore, we discuss the pathological roles of METTL1/WDR-driven m7G methylation in neurological disorders. Last, we outline a roadmap for future directions and trends of m7G modification research, particularly in the central nervous system. 

https://doi.org/10.1016/j.omtn.2023.01.003

Internal m7G methylation: A novel epitranscriptomic contributor in brain development and diseases

Neurotoxicity of nanoparticles: Insight from studies in zebrafish.

The neurodevelopmental role of dopaminergic signaling in neurological disorders.

RNA methylation is involved in multiple physiological and pathological processes. However, the role of RNA methylation in spinal cord regeneration has not been reported. In this study, we find an altered m6A (N6-methyladenosine) RNA methylation profiling following zebrafish spinal cord injury (SCI), in line with an altered transcription level of the m6A methylase Mettl3. Interestingly, many of the differential m6A-tagged genes associated with neural regeneration are hypomethylated, but their transcription levels are upregulated in SCI. Moreover, we find that METTL3 may be important for spinal cord regeneration. We also show a conserved feature of METTL3 changes in mouse SCI model, in which the expression of METTL3 is increased in both astrocytes and neural stem cells. Together, our results indicate that m6A RNA methylation is dynamic and conserved following SCI and may contribute to spinal cord regeneration.

Epitranscriptomic m6A regulation following spinal cord injury

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The neurodevelopmental role of dopaminergic signaling in neurological disorders.

Epitranscriptomic m6A regulation following spinal cord injury