Table 2 ASICs in neurologic disorders
From: Acid-sensing ion channels: potential therapeutic targets for neurologic diseases
Disease | Role of ASICs |
|---|---|
Parkinson’s disease | Lactic acidosis occurs in the brains of patients with PD. |
Amiloride helps protect against substantia nigra neuronal degeneration, inhibiting apoptosis. | |
Parkin gene mutations result in abnormal ASIC currents. | |
Huntington’s disease | ASIC1 inhibition enhances ubiquitin-proteasome system activity and reduces huntingtin-polyglutamine accumulation. |
Pain | ASIC3 is involved in: 1) primary afferent gastrointestinal visceral pain, 2) chemical nociception of the upper gastrointestinal system, and 3) mechanical nociception of the colon. |
Blocking neuronal ASIC1a expression in dorsal root ganglia may confer analgesia. | |
NSAIDs inhibit sensory neuronal ASIC expression. | |
Cerebral ischemia | Neuronal ASIC2 expression in the hypothalamus is upregulated after ischemia. |
Blockade of ASIC1a exerts a neuroprotective effect in a middle cerebral artery occlusion model. | |
Migraine | Most dural afferent nerves express ASICs. |
Multiple sclerosis | ASIC1a is upregulated in oligodendrocytes and in axons of an acute autoimmune encephalomyelitis mouse model, as well as in brain tissue from patients with multiple sclerosis. |
Blockade of ASIC1a may attenuate myelin and neuronal damage in multiple sclerosis. | |
Seizure | Intraventricular injection of PcTX-1 increases the frequency of tonic-clonic seizures. |
Low-pH stimulation increases ASIC1a inhibitory neuronal currents. | |
Malignant glioma | ASIC1a is widely expressed in malignant glial cells. |
PcTx1 or ASIC1a knock-down inhibits cell migration and cell-cycle progression in gliomas. | |
Amiloride analogue benzamil also produces cell-cycle arrest in glioblastoma. |