CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) - Volume 21, Issue 5, 2022

Age-related Neurological Disorders (ANDs) involve Neurodegenerative Diseases (NDDs), such as Alzheimer's Disease (AD), the most frequent kind of dementia in elderly people, and Parkinson's Disease (PD), and also other disorders like epilepsy and migraine. Although ANDs are multifactorial, aging is a principal risk factor for them. The common and most main pathologic features among ANDs are inflammation, oxidative stress, and misfolded proteins accumulation. Since failing brains caused by ANDs impose a notable burden on public health and their incidence is increasing, a lot of works have been conducted to overcome them. Garlic, Allium sativum, has been used for different medical purposes globally and more than thousands of publications have reported its health benefits. Garlic and aged garlic extract are considered potent anti-inflammatory and antioxidants agents and can have remarkable neuroprotective effects. This review is aimed to summarize knowledge on the pharmacotherapeutic potential of garlic and its components in ANDs.

Autism spectrum disorder (ASD) is a composite disorder of brain development with uncertain etiology and pathophysiology. Genetic factors are important in ASD causation, although environmental factors are also involved in ASD pathophysiology. Environmental factors might affect the genetic processes of brain development through the modulation of molecular pathways that might be involved with ASD. Valproic acid and propionic acid are the major environmental factors that serve as medicine and food preservative. VPA is used as an anti-epileptic medicine, but it has adverse effects on pregnant women and alters the developmental patterns of the embryo. It is a multi- targeting agent and affects 5-HT, GABA, etc. PPA is a secondary metabolite of gut microbiota that is commonly used as a food preservative. PPA plays a significant role in ASD causation by altering the several developmental molecular pathways like PTEN/Akt, mTOR/Gskβ, Cytokines activated pathways, etc., at the prenatal and neonatal stage. Moreover, ASD complexity might be increased by other important factors like vitamin A deficiency. Vitamin A is important for cortical brain development and neuronal cell differentiation. Additionally, several important genes such as RELN, Lhx2, CREB, IL-6, NMDA, BDNF, etc., are also altered in ASD and involved in brain development, central nervous system, and enteric nervous system. These genes affect neuronal differentiation, hyperactivity, oxidative stress, oxytocin, and GABA imbalance lead to improper behavior in autistic individuals. These genes are also studied in VPA and PPA ASD-like animal models. In this review, we explored the mechanical pathways that might be altered with VPA and PPA exposures at the embryonic developmental stage or neonatal developmental stage.

Alzheimer’s disease is inflating worldwide and is combatted by only a few approved drugs. At best, these drugs treat symptomatic conditions by targeting cholinesterase and N-methyl- D-aspartate receptors. Most of the clinical trials in progress are focused on developing disease-modifying agents that aim at single targets. The ‘one drug-one target’ approach is failing in the case of Alzheimer’s disease due to its labyrinth etiopathogenesis. Traditional medicinal systems like Ayurveda use a holistic approach encompassing the legion of medicinal plants exhibiting multimodal activity. Recent advances in high-throughput technologies have catapulted the research in the arena of Ayurveda, specifically in identifying plants with potent anti-Alzheimer’s disease properties and their phytochemical characterization. Nonetheless, clinical trials of very few herbal medicines are in progress. This review is a compendium of Indian plants and ayurvedic medicines against Alzheimer’s disease and their paraphernalia. A record of 230 plants that are found in India with anti-Alzheimer’s disease potential and about 500 phytochemicals from medicinal plants have been solicited with the hope of exploring the unexplored. Further, the molecular targets of phytochemicals isolated from commonly used medicinal plants, such as Acorus calamus, Bacopa monnieri, Convolvulus pluricaulis, Tinospora cordifolia and Withania somnifera, have been reviewed with respect to their multidimensional property, such as antioxidant, anti-inflammation, anti-aggregation, synaptic plasticity modulation, cognition, and memory-enhancing activity. In addition, the strengths and challenges in ayurvedic medicine that limit its use as mainstream therapy are discussed, and a framework for the development of herbal medicine has been proposed.

Acetylcholinesterase (AchE), hydrolase enzyme, regulates the hydrolysis of acetylcholine neurotransmitter in the neurons. AchE is found majorly in the central nervous system at the site of cholinergic neurotransmission. It is involved in the pathophysiology of Alzheimer’s diseasecausing dementia, cognitive impairment, behavioral and psychological symptoms. Recent findings involved the inhibition of AchE that could aid in the treatment of Alzheimer's. Many drugs of different classes are being analyzed in the clinical trials and examined for their potency. Drugs that are used in the treatment of Alzheimer’s disease are donepezil, galantamine, tacrine, rivastigmine showing major adverse effects. To overcome this, researchers work on novel drugs to elicit inhibition. This review comprises many hybrids and non-hybrid forms of heteroaromatic and nonheteroaromatic compounds that were designed and evaluated for AchE inhibition by Ellman’s method of assay. These novel compounds may assist future perspectives in the discovery of novel moieties against Alzheimer’s disease by the inhibition of AchE.

Background: Febrile Seizures (FS) are the most common seizures in children younger than 5 years. In the last decade, various coding and noncoding sequence variations of voltage-gated sodium channels SCN2A have been identified in patients with seizures, implying their genetic base. We aimed to evaluate the association between SCN2A c. G/A genetic polymorphism among Egyptian children with febrile seizure plus. Methods: The present cross-sectional study was carried out on 100 epileptic infants and children, attendants of the Neurology Unit, pediatric department, Menoufia University Hospitals (Group ). The patients were sub-classified into two groups, according to response to anti-epileptic treatment; Group a (drug responder) and Group b (drug-resistant). Evenly divided number of apparently healthy, age and gender-matched children were selected as controls (Group II). A complete history, throughout the systemic examination and radiological & metabolic assessment, whenever needed was provided, all participants were genotyped for SCN2A rs17183814 polymorphism by Restriction Fragment Length Polymorphism (PCR-RFLP). Results: Both of A allele and AA, GA genotypes of SCN2A c. 56 G/A were detected more in patients with febrile seizure plus comparison to the control group with a statistically significant difference at frequencies of 17% and 11% and 12% respectively; OR (CI95%): 10.04 (3.49-28.87) and p <0.001. On classifying epileptic patients into 2 subgroups, carriers of SCN2A rs17183814 AA genotype tended to respond poorly to Anti-epileptic Drugs (AEDs). Moreover, multivariate analysis revealed that rs17183814 A allele and positive family history of epilepsy were considered the highest predicted risk factors for the development of epilepsy; p<0.05. Conclusion: SCN2A rs17183814 (A) allele was specifically associated with developing febrile seizure plus and could modulate the patient's response to anti-epileptic medications.