Mitochondrial Ion Channels in Aging and Related Diseases

Abstract

Transport of materials and information across cellular boundaries, such as plasma, mitochondrial and nuclear membranes, happens mainly through varieties of ion channels and pumps. Various biophysical and biochemical processes play vital roles. The underlying mechanisms and associated phenomenological lipid membrane transports are linked directly or indirectly to the cell health condition. Mitochondrial membranes (mitochondrial outer membrane (MOM) and mitochondrial inner membrane (MIM)) host crucial cellular processes. Their malfunction is often found responsible for the rise of cell-originated diseases, including cancer, Alzheimer’s, neurodegenerative disease, etc. A large number of ion channels active across MOM and MIM are known to belong to vital cell-based structures found to be linked directly to cellular signaling. Hence their malfunctions are often found to contribute to abnormalities in intracellular communication, which may even be associated with the rise of various diseases. In this article, the aim is to pinpoint ion channels that are directly or indirectly linked to especially aging and related abnormalities in health conditions. An attempt has been made to address the natural structures of these channels, their mutated conditions, and the ways we may cause interventions in their malfunctioning. The malfunction of ion channel subunits, including especially various proteins, involved directly in channel formation and/or indirectly in channel stabilization, leads to the rise of various channel-specific diseases, which are known as channelopathies. Channelopathies in aging will be discussed briefly. This mini-review may be found as an important reference for drug discovery scientists dealing with aging-related diseases.

Behavior of KCNQ Channels in Neural Plasticity and Motor Disorders

“…However, the future direction of KCNQ neural mechanosensation literature ought to focus more on the clinical and translational use of these pharmacotherapeutic options, as most of the literature used to support this review was based on animal models alone. Despite this, there is strong evidence that could support the initiation of future clinical trials, especially for auditory pathologies as well as in PD [ 14 , 80 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 , 105 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 ], and developments for understanding the effects that antimicrobial agents have on these potassium ion channels [ 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 ]. Additionally, the scope of this review was on neural modulation, yet there is a growing amount of literature on the behavior of KCNQ channels in cardiac modulations as well, especially in the cellular processes involved in arrhythmia [ 26 , 27 , 28 , 29 , 139 , 140 , 141 ,…”

“…This is where the literature ought to focus in order to determine if secondary factors that are not understood in these animal models also contribute to the memory impairment (i.e., hippocampal morphology) [ 90 , 91 , 92 , 93 , 94 , 95 ]. The epileptic phenotype, in conjunction with the cognitive impairment of these genetic models, may suggest additional psychomotor exploration [ 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 ].…”

“…While this avenue of study has proven to be a promising utilization of these K + channels in dopaminergic pathways, they are perhaps better associated with the treatment of motor disorders involving the neurotransmitter dopamine. Parkinson’s disease (PD) is a neurodegenerative disorder commonly associated with the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) [ 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 ]. As a result, the loss of nigrostriatal dopamine is associated with the motor symptoms classically observed in PD, such as muscular rigidity, bradykinesia, and tremor [ 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 ].…”

“…In addition to increasing the excitability of dopaminergic neurons in the SNc, XE991 has been shown to provide neuroprotective effects as well by preventing dopaminergic neuronal death. The potent neurotoxin, 6-hydroxydopamine (6-OHDA), has been shown to replicate an irreversible state similar to PD by the destruction of dopaminergic neurons in the SNc [ 98 , 99 ]. A recent study conducted by Liu et al attempted to observe the neuroprotective effects of XE991 on 6-OHDA treated rats [ 80 ].…”

“…Currently, one of the primary treatment methods for PD includes the compound L-DOPA. Within 10 years of L-DOPA administration, many PD patients receiving this drug tend to become afflicted by hyperkinetic symptoms such as chorea, myoclonus, or dystonia [ 99 , 100 , 101 ]. In rat models of L-DOPA-induced dyskinesia (LID), it was found that retigabine significantly reduced the frequency of abnormal involuntary movements (AIM).…”