Melatonin as a cytoskeletal modulator: implications for cell physiology and disease

Abstract

: The cytoskeleton is a phylogenetically well‐preserved structure that plays a key role in cell physiology. Dynamic and differential changes in cytoskeletal organization occur in cellular processes according to the cell type and the specific function. In neurons, microtubules, microfilaments and intermediate filament (IF) rearrangements occur during axogenesis, and neurite formation which eventually differentiate into axons and dendrites to constitute synaptic patterns of connectivity. In epithelial cells, dynamic modifications occur in the three main cytoskeletal components and phosphorylation of cytoskeletal associated proteins takes place during the formation of the epithelial cell monolayer that eventually will transport water. In pathological processes such as neurodegenerative and psychiatric diseases an abnormal cytoskeletal organization occurs. Melatonin, the main product secreted by pineal gland during dark phase of the photoperiod, is capable of influencing microfilament, microtubule and IF organization by acting as a cytoskeletal modulator. In this paper we will summarize the evidence which provides the data that melatonin regulates cytoskeletal organization and we describe recent findings, which indicate that melatonin effects on microfilament rearrangements in stress fibers are involved in the mechanism by which the indole synchronizes water transport in kidney‐derived epithelial cells. In addition, we review recent data, which indicates that melatonin protects the neuro‐cytoskeletal organization from damage caused by free radicals contributing to cell survival, in addition to the already described mechanism elicited by the indole to prevent apoptosis and to scavenge free radicals. Moreover, we discuss the implications of an altered cytoskeletal organization for neurodegenerative and psychiatric illnesses and its re‐establishment by melatonin.

Therapeutic Effect of Melatonin in Experimental Uveitis

“…28,29 Several lines of evidence suggest that melatonin may act as a protective agent in ocular conditions such as photokeratitis, cataract, glaucoma, retinopathy of prematurity, and ischemia/reperfusion injury (for a review see 30 ). Besides its antioxidant effect, several other mechanisms are considered to be involved in neuroprotection induced by melatonin, including its interaction with calmodulin 31 and microtubular components, 32 blockade of intracellular Ca 2ϩ levels increase, 33 inhibition of the nitridergic pathway, 34,35 decrease in vascular endothelial growth factor levels, 36,37 and decrease in retinal glutamate synaptic concentrations, 38 among others. In this context, the aim of the present work was to analyze the therapeutic effect of melatonin in the golden hamster EIU.…”

The influence of daylight exposure on platelet 5-HT levels in patients with major depression and schizophrenia

“…Recently, melatonin has been regarded as a cytoskeletal modulator, actively participating during axogenesis and neurite formation [78]. Some neurodegenerative and psychiatric diseases such as schizophrenia, Alzheimer's and Parkinson's disease have been associated with abnormal cytoskeleton organization of neurons that loose synaptic connectivity leading to impaired neurotransmission.…”

“…Some neurodegenerative and psychiatric diseases such as schizophrenia, Alzheimer's and Parkinson's disease have been associated with abnormal cytoskeleton organization of neurons that loose synaptic connectivity leading to impaired neurotransmission. With respect to that, increased melatonin secretion would act in the context of cytoskelatal disorganisation and impaired neurite formation, providing for disease progression [78][79]. In addition, due to its cytoskeletonmodulating features, melatonin has been considered as a possible therapeutic agent for mental disorders [78].…”

“…With respect to that, increased melatonin secretion would act in the context of cytoskelatal disorganisation and impaired neurite formation, providing for disease progression [78][79]. In addition, due to its cytoskeletonmodulating features, melatonin has been considered as a possible therapeutic agent for mental disorders [78].…”

Alzheimer’s Disease: Focus on the Neuroprotective Role of Melatonin

“…Melatonin also acts directly on cells without the intervention of any of these receptors by binding to calmodulin [34]. Although the free radical scavenging action of melatonin does not involve any receptors, melatonin's stimulatory action on the formation of the antioxidant enzyme γ-glutamylcysteine synthase involves RZR/ ROR α receptors [35].…”