Calcium channels are specialized ion channels exhibiting selective permeability to calcium ions. Calcium channels, comprising voltage-dependent and ligand-gated types, are pivotal in neuronal function, with their dysregulation is implicated in various neurological disorders. This review delves into the significance of the CACNA genes, including CACNA1A, CACNA1B, CACNA1C, CACNA1D, CACNA1E, CACNA1G, and CACNA1H, in the pathogenesis of conditions such as migraine, epilepsy, cerebellar ataxia, dystonia, and cerebellar atrophy. Specifically, variants in CACNA1A have been linked to familial hemiplegic migraine and epileptic seizures, underscoring its importance in neurological disease etiology. Furthermore, different genetic variants of CACNA1B have been associated with migraine susceptibility, further highlighting the role of CACNA genes in migraine pathology. The complex relationship between CACNA gene variants and neurological phenotypes, including focal seizures and ataxia, presents a variety of clinical manifestations of impaired calcium channel function. The aim of this article was to explore the role of CACNA genes in various neurological disorders, elucidating their significance in conditions such as migraine, epilepsy, and cerebellar ataxias. Further exploration of CACNA gene variants and their interactions with molecular factors, such as microRNAs, holds promise for advancing our understanding of genetic neurological disorders.

Cathepsins, a family of lysosomal proteases, play critical roles in maintaining cellular homeostasis through protein degradation and modulation of immune responses. In the central nervous system (CNS), their functions extend beyond classical proteolysis, influencing neuroinflammation, synaptic remodeling, and neurodegeneration. Emerging evidence underscores the crucial role of microglial cathepsins in the pathophysiology of several neurological disorders. This review synthesizes current knowledge on the involvement of cathepsins in a spectrum of CNS diseases, including Parkinson’s disease, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, epilepsy, Huntington’s disease, and ischemic stroke. We highlight how specific cathepsins contribute to disease progression by modulating key pathological processes such as α-synuclein and amyloid-β clearance, tau degradation, lysosomal dysfunction, neuroinflammation, and demyelination. Notably, several cathepsins demonstrate both neuroprotective and pathogenic roles depending on disease context and expression levels. Additionally, the balance between cathepsins and their endogenous inhibitors, such as cystatins, emerges as a critical factor in CNS pathology. While cathepsins represent promising biomarkers and therapeutic targets, significant gaps remain in our understanding of their mechanistic roles across diseases. Future studies focusing on their regulation, substrate specificity, and interplay with genetic and epigenetic factors may yield novel strategies for early diagnosis and disease-modifying treatments in neurology.

Background: C3 glomerulopathies (C3G), including dense deposit disease (DDD) and C3 glomerulonephritis (C3GN), are rare kidney disorders driven by dysregulation of the alternative complement pathway. Eculizumab, a terminal complement inhibitor targeting C5, has emerged as a potential therapeutic option in these conditions. This systematic review evaluated the efficacy and safety of eculizumab in patients with C3G or DDD. Methods: Literature searches in PubMed and Cochrane databases identified case reports and case series reporting eculizumab use. Results: Only eight studies involving ten patients met the inclusion criteria. Eculizumab stabilized renal function and reduced proteinuria in most cases, especially when C5b-9 deposition was present. Histopathological improvements were variable, and recurrence after discontinuation occurred in some patients. Responses were limited in cases with alternative mechanisms of C5 activation. Conclusions: Eculizumab offers clinical benefit in select C3G and DDD patients but does not address the underlying cause of complement dysregulation. The need for long-term therapy, incomplete histologic resolution, and risk of relapse underscore the necessity of larger trials and the development of personalized treatment strategies.

Migraine is a complex neurovascular disorder with a multifactorial pathophysiology involving genetic, metabolic, and environmental factors. Increasing evidence indicates that oxidative stress plays a key role in the development of migraine; however, it is unclear whether oxidative imbalance acts primarily as a causal factor or occurs as a consequence of migraine-related processes. Oxidative stress, defined as an imbalance between reactive oxygen species production and antioxidant defense mechanisms, contributes to neuronal hyperexcitability, mitochondrial dysfunction, and neuroinflammation—key mechanisms underlying migraine pathogenesis. Studies have shown elevated markers of oxidative damage and altered antioxidant enzyme activity in migraine patients. Simultaneously, metabolic and inflammatory changes associated with migraine may further exacerbate oxidative imbalance, suggesting a bidirectional relationship. Furthermore, genetic factors such as SOD2, GPX1, and CAT significantly influence susceptibility to oxidative stress and migraine. The CALCA gene, encoding CGRP, links oxidative stress mechanisms with neurogenic inflammation and activation of the trigeminovascular system. This article reviews the current evidence regarding the role of oxidative stress in migraine and discusses its relationship to molecular and genetic mechanisms. Particular attention is given to genes involved in oxidative pathways, mitochondrial function, and inflammatory responses, which may help explain individual susceptibility and variability in clinical presentation.

Arterial hypertension remains one of the leading modifiable risk factors for cardiovascular and renal morbidity and mortality worldwide, while resistant hypertension continues to represent a major therapeutic challenge despite the widespread use of conventional antihypertensive agents. Recent advances in the understanding of hypertension pathophysiology have enabled the development of novel pharmacological strategies targeting previously unexplored mechanisms. This review summarizes recently approved and emerging drugs for hypertension, with particular emphasis on agents acting on the renin–angiotensin–aldosterone system (RAAS), endothelin pathway, aldosterone synthesis, and RNA interference technology. Novel approaches include modulation of the ACE2/angiotensin-(1–7)/Mas receptor axis, inhibition of aminopeptidase A, and targeting tissue-specific RAAS activity, aiming to counteract the deleterious effects of classical RAAS activation. Dual endothelin receptor antagonists, particularly aprocitentan, have demonstrated significant and sustained blood pressure reduction in resistant hypertension with improved tolerability compared with earlier endothelin receptor antagonists. Highly selective aldosterone synthase inhibitors, including baxdrostat, lorundrostat, vicadrostat, and dexfadrostat, provide effective blood pressure lowering while minimizing cortisol suppression associated with previous agents, although hyperkalemia remains an important adverse effect. Small interfering RNA (siRNA)-based therapies represent an innovative therapeutic class, with zilebesiran producing prolonged suppression of angiotensinogen synthesis and sustained antihypertensive effects after infrequent subcutaneous administration. Collectively, these therapies offer promising alternatives for patients with uncontrolled or resistant hypertension and may provide additional cardiovascular and renal protection beyond blood pressure reduction. Nevertheless, many of these agents remain under clinical investigation, and further large-scale, long-term studies are required to establish their safety, cost-effectiveness, and impact on cardiovascular outcomes before their routine incorporation into clinical practice.