Signaling Through Actin to Regulate Spine Formation and Function

Okada, Hirokazu; Soderling, Scott H.

doi:10.2174/1874082000903010097

Cited by 2 publications

(4 citation statements)

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“…However, the role of cytoskeletal protein actin in the manifestation of NDs have been far from understood. Actin is reported to be the driving force in controlling synaptic plasticity and maintaining the structural integrity of the synapses ( Kim and Lisman, 1999 ; Luo, 2002 ; Fukazawa et al, 2003 ; Bourne and Harris, 2008 ; Okada and Soderling, 2009 ). It functions by changing its morphology in response to different types of neural activity ( Svennberg, 2006 ; Gordon-Weeks and Fournier, 2014 ; Spence and Soderling, 2015 ; Szabó et al, 2016 ; Pelucchi et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

“…It functions by changing its morphology in response to different types of neural activity ( Svennberg, 2006 ; Gordon-Weeks and Fournier, 2014 ; Spence and Soderling, 2015 ; Szabó et al, 2016 ; Pelucchi et al, 2020 ). Defects in the regulation of actin protein is one of the contributing factors leading to neurological disorders ( Kim and Lisman, 1999 ; Luo, 2002 ; Bourne and Harris, 2008 ; Okada and Soderling, 2009 ).…”

Section: Introductionmentioning

confidence: 99%

“…Mis-regulated actin in mature neurons has been implicated in various mental illnesses such as intellectual disability and schizophrenia ( Ogawa and Rasband, 2008 ). Actin polymerization dynamics has a major role in sustaining the morphology of the spine and is associated with long-term memory via activation of long-term potentiation (LTP) or long-term depression (LTD) of excitatory signal transmission ( Kim and Lisman, 1999 ; Luo, 2002 ; Bourne and Harris, 2008 ; Okada and Soderling, 2009 ). Also, actin rods are involved in the progression of axonal sensory neuropathy: a condition where neurons are damaged as observed in frataxin-deficient dorsal root ganglion (DRG) neurons ( Muñoz-Lasso et al, 2020a ).…”

Section: Introductionmentioning

confidence: 99%

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Ofloxacin as a Disruptor of Actin Aggresome “Hirano Bodies”: A Potential Repurposed Drug for the Treatment of Neurodegenerative Diseases

Pathak

Parkar

Tripathi

et al. 2020

Front. Aging Neurosci.

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There is a growing number of aging populations that are more prone to the prevalence of neuropathological disorders. Two major diseases that show a late onset of the symptoms include Alzheimer’s disorder (AD) and Parkinson’s disorder (PD), which are causing an unexpected social and economic impact on the families. A large number of researches in the last decade have focused upon the role of amyloid precursor protein, Aβ-plaque, and intraneuronal neurofibrillary tangles (tau-proteins). However, there is very few understanding of actin-associated paracrystalline structures formed in the hippocampus region of the brain and are called Hirano bodies. These actin-rich inclusion bodies are known to modulate the synaptic plasticity and employ conspicuous effects on long-term potentiation and paired-pulse paradigms. Since the currently known drugs have very little effect in controlling the progression of these diseases, there is a need to develop therapeutic agents, which can have improved efficacy and bioavailability, and can transport across the blood–brain barrier. Moreover, finding novel targets involving compound screening is both laborious and is an expensive process in itself followed by equally tedious Food and Drug Administration (FDA) approval exercise. Finding alternative functions to the already existing FDA-approved molecules for reversing the progression of age-related proteinopathies is of utmost importance. In the current study, we decipher the role of a broad-spectrum general antibiotic (Ofloxacin) on actin polymerization dynamics using various biophysical techniques like right-angle light scattering, dynamic light scattering, circular dichroism spectrometry, isothermal titration calorimetry, scanning electron microscopy, etc. We have also performed in silico docking studies to deduce a plausible mechanism of the drug binding to the actin. We report that actin gets disrupted upon binding to Ofloxacin in a concentration-dependent manner. We have inferred that Ofloxacin, when attached to a drug delivery system, can act as a good candidate for the treatment of neuropathological diseases.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Ofloxacin as a Disruptor of Actin Aggresome “Hirano Bodies”: A Potential Repurposed Drug for the Treatment of Neurodegenerative Diseases

Pathak

Parkar

Tripathi

et al. 2020

Front. Aging Neurosci.

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“…Lastly, the recent research of BDNF for the development of new therapies, in particular, against depression is discussed. ends of actins, whereas others exhibit opposite roles in the capping mechanism, or promote filament polymerization by the nucleation of new filaments [30]. This balancing mechanism is crucial for rapid control of actin dynamics within the spines.…”

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confidence: 99%

BDNF and Synaptic Plasticity: The Recent Cell Biology for Understanding of Brain Disorders

Mizui¹

2013

Clinic Pharmacol Biopharmaceut

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IntroductionThe brain exerts considerable structural and functional plasticity [1][2][3]. As an important interface between neurons, synapses are required for computation of circuits and information processing. Accumulating evidence indicates that once formed, synapses and dendrites can be maintained for long periods of time. However, they are eliminated or rewired to respond to environmental changes, as reported by Walsh and Lichtman (2003) [4]. The cell biology of neurons has been developed to the understanding of pathological mechanisms of brain disorders. This review article will pay an attention to the biological and pathological role of BDNF, which modulate synaptic plasticity in adult brain because this knowledge could prove beneficial for the development of new therapies against brain diseases. Dendritic spines are actin-rich structures, which are part of most excitatory synapses in the central nervous systems. Recent studies have shown that the morphological plasticity of the spine plays a crucial role in higher brain functions, such as learning and memory. This review focuses on recent advances in the research of dendrite spines, synaptic plasticity, and BDNF. Lastly, we will introduce recent reports demonstrating the role of BDNF in depression. Dendrite SpinesThe majority of excitatory synapses develop small protrusions on dendrites, called dendrite spines, which form the main platforms of synaptic input for neurons. Neurotransmitter receptors are largely localized at the surface of spines to counteract the presynaptic structure, axon terminals. Previously, consensus was that spine morphology is controlled for higher brain functions, such as learning and memory. Indeed, this notion has been supported by a significant number of studies. The strength of synaptic activity is controlled by the size and number of dendritic spines [5,6]. Activity-dependent remodeling and stability of spine structures is an important cellular mechanism for the maintenance and refinement of neuronal circuits [7,8]. Developing brain spines are structurally dynamic. Conversely, stable spines predominate during adult stages [2]. Interestingly, imaging studies demonstrate experience-dependent structural alterations of spines in animals [6,8], and spine genesis has a salient association with human cognitive function [9]. Moreover, autopsy studies of patients with dementia indicated a correlation between brain dysfunction and abnormal spine morphology [10,11]. Although synaptic function cannot be assessed from spine morphology, the regulatory mechanisms of spine morphogenesis, and the dynamics of spine morphology would provide insight into higher brain functions and their disorders.Dendritic spines are actin-rich protrusions [12,13] and highly dynamic [14]. The dynamics are controlled by the architecture of their actin cytoskeleton [15]. The formation, maturation, and plasticity of spines depend on actin cytoskeleton remodeling [16,17]. Many of the key molecules controlling this process are members of the Rhofamily of small GTPases...

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Signaling Through Actin to Regulate Spine Formation and Function

Cited by 2 publications

References 142 publications

Ofloxacin as a Disruptor of Actin Aggresome “Hirano Bodies”: A Potential Repurposed Drug for the Treatment of Neurodegenerative Diseases

Ofloxacin as a Disruptor of Actin Aggresome “Hirano Bodies”: A Potential Repurposed Drug for the Treatment of Neurodegenerative Diseases

BDNF and Synaptic Plasticity: The Recent Cell Biology for Understanding of Brain Disorders

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