keyword
https://read.qxmd.com/read/38491338/role-of-cytoskeletal-elements-in-regulation-of-synaptic-functions-implications-toward-alzheimer-s-disease-and-phytochemicals-based-interventions
#1
REVIEW
Harkomal Verma, Sharanjot Kaur, Sukhchain Kaur, Prabhakar Gangwar, Monisha Dhiman, Anil Kumar Mantha
Alzheimer's disease (AD), a multifactorial disease, is characterized by the accumulation of neurofibrillary tangles (NFTs) and amyloid beta (Aβ) plaques. AD is triggered via several factors like alteration in cytoskeletal proteins, a mutation in presenilin 1 (PSEN1), presenilin 2 (PSEN2), amyloid precursor protein (APP), and post-translational modifications (PTMs) in the cytoskeletal elements. Owing to the major structural and functional role of cytoskeletal elements, like the organization of axon initial segmentation, dendritic spines, synaptic regulation, and delivery of cargo at the synapse; modulation of these elements plays an important role in AD pathogenesis; like Tau is a microtubule-associated protein that stabilizes the microtubules, and it also causes inhibition of nucleo-cytoplasmic transportation by disrupting the integrity of nuclear pore complex...
March 16, 2024: Molecular Neurobiology
https://read.qxmd.com/read/38451813/cofilactin-rod-formation-mediates-inflammation-induced-neurite-degeneration
#2
JOURNAL ARTICLE
Gökhan Uruk, Ebony Mocanu, Alisa E Shaw, James R Bamburg, Raymond A Swanson
Stroke, trauma, and neurodegenerative disorders cause loss of neurites (axons and dendrites) in addition to neuronal death. Neurite loss may result directly from a primary insult, secondary to parental neuron death, or secondary to a post-injury inflammatory response. Here, we use lipopolysaccharide and the alarmin S100β to selectively evaluate neurite loss caused by the inflammatory response. Activation of microglia and infiltrating macrophages by these stimuli causes neurite loss that far exceeds neuronal death, both in vitro and in vivo...
March 6, 2024: Cell Reports
https://read.qxmd.com/read/38441532/nudc-is-critical-for-rod-photoreceptor-function-maintenance-and-survival
#3
JOURNAL ARTICLE
Mary Anne Garner, Meredith G Hubbard, Evan R Boitet, Seth T Hubbard, Anushree Gade, Guoxin Ying, Bryan W Jones, Wolfgang Baehr, Alecia K Gross
NUDC (nuclear distribution protein C) is a mitotic protein involved in nuclear migration and cytokinesis across species. Considered a cytoplasmic dynein (henceforth dynein) cofactor, NUDC was shown to associate with the dynein motor complex during neuronal migration. NUDC is also expressed in postmitotic vertebrate rod photoreceptors where its function is unknown. Here, we examined the role of NUDC in postmitotic rod photoreceptors by studying the consequences of a conditional NUDC knockout in mouse rods (rNudC-/- )...
March 15, 2024: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/38299702/protein-complexes-from-mouse-and-chick-brain-that-interact-with-phospho-kxgs-motif-tau-microtubule-associated-protein-antibody
#4
JOURNAL ARTICLE
Danielle Davies, Ariel T Arthur, Hayden L Aitken, Ben Crossett, Claire Goldsbury
Mouse monoclonal 12E8 antibody, that recognises conserved serine phosphorylated KXGS motifs in the microtubule binding domains of tau/tau-like microtubule associated proteins (MAPs), shows elevated binding in brain during normal embryonic development (mammals and birds) and at the early stages of human Alzheimers Disease (AD). It also labels ADF/cofilin-actin rods that form in neurites during exposure to stressors. We aimed to identify direct and indirect 12E8 binding proteins in postnatal mouse brain and embryonic chick brain by immunoprecipitation (IP), mass spectrometry and immunofluorescence...
February 1, 2024: Biology Open
https://read.qxmd.com/read/38299375/bioenergetic-and-excitotoxic-determinants-of-cofilactin-rod-formation
#5
JOURNAL ARTICLE
Nguyen Mai, Long Wu, Gökhan Uruk, Ebony Mocanu, Raymond A Swanson
Cofilactin rods (CARs), which are 1:1 aggregates of cofilin-1 and actin, lead to neurite loss in ischemic stroke and other disorders. The biochemical pathways driving CAR formation are well-established, but how these pathways are engaged under ischemic conditions is less clear. Brain ischemia produces both ATP depletion and glutamate excitotoxicity, both of which have been shown to drive CAR formation in other settings. Here, we show that CARs are formed in cultured neurons exposed to ischemia-like conditions: oxygen-glucose deprivation (OGD), glutamate, or oxidative stress...
February 1, 2024: Journal of Neurochemistry
https://read.qxmd.com/read/38256947/cofilin-inhibitor-improves-neurological-and-cognitive-functions-after-intracerebral-hemorrhage-by-suppressing-endoplasmic-reticulum-stress-related-neuroinflammation
#6
JOURNAL ARTICLE
Daniyah A Almarghalani, Ghaith A Bahader, Mohammad Ali, L M Viranga Tillekeratne, Zahoor A Shah
Neuroinflammation after intracerebral hemorrhage (ICH) is a crucial factor that determines the extent of the injury. Cofilin is a cytoskeleton-associated protein that drives neuroinflammation and microglia activation. A novel cofilin inhibitor (CI) synthesized and developed in our lab has turned out to be a potential therapeutic agent for targeting cofilin-mediated neuroinflammation in an in vitro model of ICH and traumatic brain injury. The current study aims to examine the therapeutic potential of CI in a mouse collagenase model of ICH and examine the neurobehavioral outcomes and its mechanism of action...
January 15, 2024: Pharmaceuticals
https://read.qxmd.com/read/38255199/chemokine-receptor-antagonists-prevent-and-reverse-cofilin-actin-rod-pathology-and-protect-synapses-in-cultured-rodent-and-human-ipsc-derived-neurons
#7
JOURNAL ARTICLE
Thomas B Kuhn, Laurie S Minamide, Lubna H Tahtamouni, Sydney A Alderfer, Keifer P Walsh, Alisa E Shaw, Omar Yanouri, Henry J Haigler, Michael R Ruff, James R Bamburg
Synapse loss is the principal cause of cognitive decline in Alzheimer's disease (AD) and related disorders (ADRD). Synapse development depends on the intricate dynamics of the neuronal cytoskeleton. Cofilin, the major protein regulating actin dynamics, can be sequestered into cofilactin rods, intra-neurite bundles of cofilin-saturated actin filaments that can disrupt vesicular trafficking and cause synaptic loss. Rods are a brain pathology in human AD and mouse models of AD and ADRD. Eliminating rods is the focus of this paper...
January 1, 2024: Biomedicines
https://read.qxmd.com/read/38076848/nudc-is-critical-for-rod-photoreceptor-function-maintenance-and-survival
#8
Mary Anne Garner, Meredith G Hubbard, Evan R Boitet, Seth T Hubbard, Anushree Gade, Guoxin Ying, Bryan W Jones, Wolfgang Baehr, Alecia K Gross
UNLABELLED: NUDC ( nu clear d istribution protein C) is a mitotic protein involved in nuclear migration and cytokinesis across species. Considered a cytoplasmic dynein (henceforth dynein) cofactor, NUDC was shown to associate with the dynein motor complex during neuronal migration. NUDC is also expressed in postmitotic vertebrate rod photoreceptors where its function is unknown. Here, we examined the role of NUDC in postmitotic rod photoreceptors by studying the consequences of a conditional NUDC knockout in mouse rods (r NudC -/- )...
November 29, 2023: bioRxiv
https://read.qxmd.com/read/38001943/characterization-of-a-human-neuronal-culture-system-for-the-study-of-cofilin-actin-rod-pathology
#9
JOURNAL ARTICLE
Lubna H Tahtamouni, Sydney A Alderfer, Thomas B Kuhn, Laurie S Minamide, Soham Chanda, Michael R Ruff, James R Bamburg
Cofilactin rod pathology, which can initiate synapse loss, has been extensively studied in rodent neurons, hippocampal slices, and in vivo mouse models of human neurodegenerative diseases such as Alzheimer's disease (AD). In these systems, rod formation induced by disease-associated factors, such as soluble oligomers of Amyloid-β (Aβ) in AD, utilizes a pathway requiring cellular prion protein (PrPC ), NADPH oxidase (NOX), and cytokine/chemokine receptors (CCR5 and/or CXCR4). However, rod pathways have not been systematically assessed in a human neuronal model...
October 31, 2023: Biomedicines
https://read.qxmd.com/read/37873064/optoprofilin-a-single-component-biosensor-of-applied-cellular-stress
#10
Noah Mann, Jahiem Hill, Kenneth Wang, Robert M Hughes
The actin cytoskeleton is a biosensor of cellular stress and a potential prognosticator of human disease. In particular, aberrant cytoskeletal structures such as cofilin-actin rods and stress granules formed in response to energetic and oxidative stress are closely linked to neurodegenerative diseases such as Alzheimer's, Parkinson's, and ALS. Whether these cytoskeletal phenomena can be harnessed for the development of biosensors for cytoskeletal dysfunction and, by extension, neurodegenerative disease progression, remains an open question...
October 4, 2023: bioRxiv
https://read.qxmd.com/read/37190062/spatiotemporal-cofilin-signaling-microglial-activation-neuroinflammation-and-cognitive-impairment-following-hemorrhagic-brain-injury
#11
JOURNAL ARTICLE
Daniyah A Almarghalani, Xiaojin Sha, Robert E Mrak, Zahoor A Shah
Intracerebral hemorrhage (ICH) is a significant health concern associated with high mortality. Cofilin plays a crucial role in stress conditions, but its signaling following ICH in a longitudinal study is yet to be ascertained. In the present study, we examined the cofilin expression in human ICH autopsy brains. Then, the spatiotemporal cofilin signaling, microglia activation, and neurobehavioral outcomes were investigated in a mouse model of ICH. Human autopsy brain sections from ICH patients showed increased intracellular cofilin localization within microglia in the perihematomal area, possibly associated with microglial activation and morphological changes...
April 13, 2023: Cells
https://read.qxmd.com/read/36513938/visualizing-cofilin-actin-filaments-by-immunofluorescence-and-cryoem-essential-steps-for-observing-cofilactin-in-cells
#12
JOURNAL ARTICLE
Laurie S Minamide, Ryan Hylton, Matthew Swulius, James R Bamburg
Fluorescence microscopy of cytoskeletal proteins in situ using immunolabeling, fluorescent reagents, or expression of tagged proteins has been a common practice for decades but often with too little regard for what might not be visualized. This is especially true for assembled filamentous actin (F-actin), for which binding of fluorescently labeled phalloidin is taken as the gold standard for its quantification even though it is well known that F-actin saturated with cofilin (cofilactin) binds neither fluorescently labeled phalloidin nor genetically encoded F-actin reporters, such as LifeAct...
2023: Methods in Molecular Biology
https://read.qxmd.com/read/36212686/cytoskeletal-dysregulation-and-neurodegenerative-disease-formation-monitoring-and-inhibition-of-cofilin-actin-rods
#13
REVIEW
Anna I Wurz, Anna M Schulz, Collin T O'Bryant, Josephine F Sharp, Robert M Hughes
The presence of atypical cytoskeletal dynamics, structures, and associated morphologies is a common theme uniting numerous diseases and developmental disorders. In particular, cytoskeletal dysregulation is a common cellular feature of Alzheimer's disease, Parkinson's disease, and Huntington's disease. While the numerous activators and inhibitors of dysregulation present complexities for characterizing these elements as byproducts or initiators of the disease state, it is increasingly clear that a better understanding of these anomalies is critical for advancing the state of knowledge and plan of therapeutic attack...
2022: Frontiers in Cellular Neuroscience
https://read.qxmd.com/read/35994830/formation-of-actin-cofilin-rods-by-depletion-forces
#14
JOURNAL ARTICLE
Kohki Takayama, Kota Matsuda, Hiroshi Abe
Various stress conditions induce the formation of actin-cofilin rods in either the nucleus or the cytoplasm, although the mechanism of rod formation is unclear. In this study, we constituted actin-cofilin rods using purified actin, cofilin and actin interacting protein 1 (AIP1) in the presence of a physiological buffer containing a crowding agent, 0.8% methylcellulose (MC), which led to bundled actin filaments formed by depletion forces. Most of the F-actin bundles formed with methylcellulose were linear, whereas cofilin-bound F-actin bundles often had bent, looped, and often ring-like shapes...
August 13, 2022: Biochemical and Biophysical Research Communications
https://read.qxmd.com/read/35553709/derivation-of-actin-binding-peptides-from-a-cofilin-scaffold-a-rational-approach
#15
JOURNAL ARTICLE
Collin T O'Bryant, Jordan M Hardeman, Riley N Bessetti, Karen A Litwa, Robert M Hughes
Actin-binding peptides and proteins have numerous applications in the control and monitoring of cellular dynamics. This is effectively demonstrated by the wide usage of protein fusions containing the actin-binding peptide LifeAct and fluorescent proteins for live cell imaging. Despite their popularity, there remains a need for a new generation of actin-binding probes that are largely orthogonal to cellular processes. We propose that this need could be met by a rational deconstructive approach to well-characterized actin-binding peptides such as cofilin...
May 2022: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/35492354/chaperonin-containing-tcp1-subunit-5-protects-against-the-effect-of-mer-receptor-tyrosine-kinase-knockdown-in-retinal-pigment-epithelial-cells-by-interacting-with-filamentous-actin-and-activating-the-lim-kinase-1-cofilin-pathway
#16
JOURNAL ARTICLE
Lujia Feng, Haichun Li, Yong Du, Ting Zhang, Yingting Zhu, Zhidong Li, Ling Zhao, Xing Wang, Gongpei Wang, Linbin Zhou, Zhaorong Jiang, Zheng Liu, Zhancong Ou, Yuwen Wen, Yehong Zhuo
Retinitis pigmentosa (RP), characterized by the gradual loss of rod and cone photoreceptors that eventually leads to blindness, is the most common inherited retinal disorder, affecting more than 2.5 million people worldwide. However, the underlying pathogenesis of RP remains unclear and there is no effective cure for RP. Mutations in the Mer receptor tyrosine kinase ( MERTK ) gene induce the phagocytic dysfunction of retinal pigment epithelium (RPE) cells, leading to RP. Studies have indicated that filamentous actin (F-actin)-which is regulated by chaperonin-containing TCP1 subunit 5 (CCT5)-plays a vital role in phagocytosis in RPE cells...
2022: Frontiers in Medicine
https://read.qxmd.com/read/35319840/-electroacupuncture-promotes-the-repair-of-neurological-function-in-ischemic-stroke-rats-by-inhi-biting-cofilin-rod-formation
#17
JOURNAL ARTICLE
Bin Chen, Xiao-Yong Zhong, Xiao-Fang You, Wan-Qing Lin
OBJECTIVE: To observe the effect of electroacupuncture (EA) on modified neurological severity score (mNSS), cerebral infarction volume, expression of Lim domain kinase-1 (LIMK1) and slingshot homolog-1 (SSH1) proteins, Cofilin rod formation and neural cell apoptosis in rats with ischemic stroke (IS), so as to explore its mechanisms underlying improvement of IS. METHODS: Male SD rats were randomly divided into normal, model and EA groups, with 13 rats in each group...
March 25, 2022: Zhen Ci Yan Jiu, Acupuncture Research
https://read.qxmd.com/read/34869330/formation-of-cytoplasmic-actin-cofilin-rods-is-triggered-by-metabolic-stress-and-changes-in-cellular-ph
#18
JOURNAL ARTICLE
Hellen C Ishikawa-Ankerhold, Sophie Kurzbach, Arzu S Kinali, Annette Müller-Taubenberger
Actin dynamics plays a crucial role in regulating essential cell functions and thereby is largely responsible to a considerable extent for cellular energy consumption. Certain pathological conditions in humans, like neurological disorders such as Alzheimer's disease or amyotrophic lateral sclerosis (ALS) as well as variants of nemaline myopathy are associated with cytoskeletal abnormalities, so-called actin-cofilin rods. Actin-cofilin rods are aggregates consisting mainly of actin and cofilin, which are formed as a result of cellular stress and thereby help to ensure the survival of cells under unfavorable conditions...
2021: Frontiers in Cell and Developmental Biology
https://read.qxmd.com/read/34862840/a-homozygous-cap2-pathogenic-variant-in-a-neonate-presenting-with-rapidly-progressive-cardiomyopathy-and-nemaline-rods
#19
Sharavana Gurunathan, Jessica Sebastian, Jennifer Baker, Hoda Z Abdel-Hamid, Shawn C West, Brian Feingold, Vivek Peche, Miguel Reyes-Múgica, Suneeta Madan-Khetarpal, Jeffrey Field
Nemaline Myopathy (NM) is a disorder of skeletal muscles caused by mutations in sarcomere proteins and characterized by accumulation of microscopic rod or thread-like structures (nemaline bodies) in skeletal muscles. Patients diagnosed with both NM and infantile cardiomyopathy are very rare. A male infant presented, within the first few hours of life, with severe dilated cardiomyopathy, biventricular dysfunction and left ventricular noncompaction. A muscle biopsy on the 8th day of life from the right sternocleidomastoid muscle identified nemaline rods...
December 4, 2021: American Journal of Medical Genetics. Part A
https://read.qxmd.com/read/34685706/cofilin-and-actin-dynamics-multiple-modes-of-regulation-and-their-impacts-in-neuronal-development-and-degeneration
#20
REVIEW
James R Bamburg, Laurie S Minamide, O'Neil Wiggan, Lubna H Tahtamouni, Thomas B Kuhn
Proteins of the actin depolymerizing factor (ADF)/cofilin family are ubiquitous among eukaryotes and are essential regulators of actin dynamics and function. Mammalian neurons express cofilin-1 as the major isoform, but ADF and cofilin-2 are also expressed. All isoforms bind preferentially and cooperatively along ADP-subunits in F-actin, affecting the filament helical rotation, and when either alone or when enhanced by other proteins, promotes filament severing and subunit turnover. Although self-regulating cofilin-mediated actin dynamics can drive motility without post-translational regulation, cells utilize many mechanisms to locally control cofilin, including cooperation/competition with other proteins...
October 12, 2021: Cells
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