Browsing by Subject "Chaperones"

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    Correction to: Multidimensional insights into the repeated electromagnetic field stimulation and biosystems interaction in aging and age-related diseases
    (BMC, 2022-09-09) Perez, Felipe P.; Bandeira, Joseph P.; Perez Chumbiauca, Cristina N.; Lahiri, Debomoy K.; Morisaki, Jorge; Rizkalla, Maher; Medicine, School of Medicine
    Correction to: Journal of Biomedical Science (2022) 29:39 https://doi.org/10.1186/s12929-022-00825-y
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    Multidimensional insights into the repeated electromagnetic field stimulation and biosystems interaction in aging and age-related diseases
    (BMC, 2022-06-13) Perez, Felipe P.; Bandeira, Joseph P.; Perez Chumbiauca, Cristina N.; Lahiri, Debomoy K.; Morisaki, Jorge; Rizkalla, Maher; Medicine, School of Medicine
    We provide a multidimensional sequence of events that describe the electromagnetic field (EMF) stimulation and biological system interaction. We describe this process from the quantum to the molecular, cellular, and organismal levels. We hypothesized that the sequence of events of these interactions starts with the oscillatory effect of the repeated electromagnetic stimulation (REMFS). These oscillations affect the interfacial water of an RNA causing changes at the quantum and molecular levels that release protons by quantum tunneling. Then protonation of RNA produces conformational changes that allow it to bind and activate Heat Shock Transcription Factor 1 (HSF1). Activated HSF1 binds to the DNA expressing chaperones that help regulate autophagy and degradation of abnormal proteins. This action helps to prevent and treat diseases such as Alzheimer's and Parkinson's disease (PD) by increasing clearance of pathologic proteins. This framework is based on multiple mathematical models, computer simulations, biophysical experiments, and cellular and animal studies. Results of the literature review and our research point towards the capacity of REMFS to manipulate various networks altered in aging (Reale et al. PloS one 9, e104973, 2014), including delay of cellular senescence (Perez et al. 2008, Exp Gerontol 43, 307-316) and reduction in levels of amyloid-β peptides (Aβ) (Perez et al. 2021, Sci Rep 11, 621). Results of these experiments using REMFS at low frequencies can be applied to the treatment of patients with age-related diseases. The use of EMF as a non-invasive therapeutic modality for Alzheimer's disease, specifically, holds promise. It is also necessary to consider the complicated and interconnected genetic and epigenetic effects of the REMFS-biological system's interaction while avoiding any possible adverse effects.
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    Uncoupling of p97 ATPase activity has a dominant negative effect on protein extraction
    (Springer Nature, 2019-07-17) Rycenga, Halley B.; Wolfe, Kelly B.; Yeh, Elizabeth S.; Long, David T.; Pharmacology & Toxicology, IU School of Medicine
    p97 is a highly abundant, homohexameric AAA+ ATPase that performs a variety of essential cellular functions. Characterized as a ubiquitin-selective chaperone, p97 recognizes proteins conjugated to K48-linked polyubiquitin chains and promotes their removal from chromatin and other molecular complexes. Changes in p97 expression or activity are associated with the development of cancer and several related neurodegenerative disorders. Although pathogenic p97 mutations cluster in and around p97's ATPase domains, mutant proteins display normal or elevated ATPase activity. Here, we show that one of the most common p97 mutations (R155C) retains ATPase activity, but is functionally defective. p97-R155C can be recruited to ubiquitinated substrates on chromatin, but is unable to promote substrate removal. As a result, p97-R155C acts as a dominant negative, blocking protein extraction by a similar mechanism to that observed when p97's ATPase activity is inhibited or inactivated. However, unlike ATPase-deficient proteins, p97-R155C consumes excess ATP, which can hinder high-energy processes. Together, our results shed new insight into how pathogenic mutations in p97 alter its cellular function, with implications for understanding the etiology and treatment of p97-associated diseases.