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<p>Epilepsy is a neurological disorder characterised by aberrant synchronised neuronal activity in the brain and affects millions of people globally. The renin-angiotensin system (RAS) has been implicated in epilepsy pathophysiology, with angiotensin receptors playing pivotal role in seizure modulation and neuroprotection. This review explores the angiotensin-epilepsy axis, and elaborates upon the role of angiotensin receptors (AT-1, AT-2, AT-4, and Mas) in the CNS. AT-1 receptor stimulation is related to neuroinflammation, oxidative stress, and propagation of seizures, whereas their blockade by angiotensin receptor blockers (ARBs) demonstrated anticonvulsant and neuroprotective effects in preclinical model. AT-2 receptor activation down-regulates pro-inflammatory cytokines &amp; protects the blood-brain barrier and induces neuronal survival and differentiation. They also interact with the AT-4 receptor identified as insulin-regulated amino peptidase (IRAP), a receptor that is implicated in its neuroinflammatory modulation, oxidative stress, and excitotoxicity. Against this background, the Mas receptor was recognized as the receptor for angiotensin-(1–7), leading to vasodilator, anti-inflammatory and anti-oxidant effects that oppose angiotensin II actions. This intricate interplay between these receptors and ligands accompanies the dynamic regulation of neurotransmitters, neuroinflammation, and neuroprotection in epileptic seizures. The role of the RAS in epilepsy may present new therapeutic targets in addressing this devastating disorder, especially in patients with coexisting cardiovascular illnesses.</p>

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Role of the renin-angiotensin pathway in epilepsy: a strategy for its management by drug repurposing

  • 期刊论文

  • 发表日期：

    2025年7月10日

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  • Rakesh Bagle,
  • Shubham Teli,
  • Bhushan Khombare,
  • Mallappa Shalavadi

摘要

Epilepsy is a neurological disorder characterised by aberrant synchronised neuronal activity in the brain and affects millions of people globally. The renin-angiotensin system (RAS) has been implicated in epilepsy pathophysiology, with angiotensin receptors playing pivotal role in seizure modulation and neuroprotection. This review explores the angiotensin-epilepsy axis, and elaborates upon the role of angiotensin receptors (AT-1, AT-2, AT-4, and Mas) in the CNS. AT-1 receptor stimulation is related to neuroinflammation, oxidative stress, and propagation of seizures, whereas their blockade by angiotensin receptor blockers (ARBs) demonstrated anticonvulsant and neuroprotective effects in preclinical model. AT-2 receptor activation down-regulates pro-inflammatory cytokines & protects the blood-brain barrier and induces neuronal survival and differentiation. They also interact with the AT-4 receptor identified as insulin-regulated amino peptidase (IRAP), a receptor that is implicated in its neuroinflammatory modulation, oxidative stress, and excitotoxicity. Against this background, the Mas receptor was recognized as the receptor for angiotensin-(1–7), leading to vasodilator, anti-inflammatory and anti-oxidant effects that oppose angiotensin II actions. This intricate interplay between these receptors and ligands accompanies the dynamic regulation of neurotransmitters, neuroinflammation, and neuroprotection in epileptic seizures. The role of the RAS in epilepsy may present new therapeutic targets in addressing this devastating disorder, especially in patients with coexisting cardiovascular illnesses.