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Unilateral Ex Vivo Gene Therapy by GDNF in Neurodegenerative Diseases
Published in Yashwant V. Pathak, Gene Delivery Systems, 2022
Sonia Barua, Yashwant V. Pathak
Nerve growth factor (NGF) is a neurotrophic factor and comes under the transforming growth factor-β superfamily [4]. NGF mainly controls cell growth and maintains the cell proliferation and survival rate [3–4]. Studies have reported that NGF has been shown to act as a potential therapeutic agent for AD. Delivery of NGF in nerve cells of Alzheimer’s patients exhibited a positive effect on the basal forebrain cholinergic neurons, which decline in AD patients [5–9]. Glial cell line–derived neurotrophic factor (GDNF) is a neurotrophic factor whose functions is to protect the neurons from degeneration. GDNF was initially recognized as a survival factor for dopaminergic neurons. It is widely distributed in the rat and human CNS, but is expressed highly in the principal pyramidal neurons and the dentate gyrus (DG) granule cells. GDNF has been shown to increase the dopaminergic function in patients with PD [7–8]. These findings have drawn much attention in clinical trials of GDNF therapy for the restoration of PD patients. Gene therapy is a potential agent to deliver the GDNF to the targeted neurons. In transplantation, ex vivo cell-based gene delivery of GDNF shows an advantage in that it removes cells if untoward effects occur [7–9] (Figure 9.1). In addition, the development of cell lines is considered a novel strategy for transplantation into the damaged CNS (cell therapy), which favors the expression and delivery of molecules with therapeutic potential (ex vivo gene therapy) by limiting the challenges associated with the in vivo technique.
Organic Nanocarriers for Brain Drug Delivery
Published in Carla Vitorino, Andreia Jorge, Alberto Pais, Nanoparticles for Brain Drug Delivery, 2021
Marlene Lúcio, Carla M. Lopes, Eduarda Fernandes, Hugo Gonẹalves, Maria Elisabete C. D. Real Oliveira
Glial cell-derived neurotrophic factor (GDNF) is a small protein which promotes the survival of many types of neurons [97]. Accordingly, ongoing studies have shown that GDNF can promote the growth, regeneration and survival of substantia nigra dopamine neurons, preventing the progression of PD when given at an early stage of the disease [83, 97]. In this regard, the liposomal formulation composed by 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), Chol and stearylamine (SA) loaded with GDNF was i.n. administered in rats. GDNF demonstrated neurotrophic and neuroprotective effects of GDNF protein in the brain of rats either in GDNF not encapsulated or in GDNF encapsulated in liposomes. However, the liposomal formulation may have the advantage of a protective effect on the protein, preventing it from degrading [98].
Biomedical Insights of Lipid- and Protein- Based Biocomposites
Published in Shakeel Ahmed, Saiqa Ikram, Suvardhan Kanchi, Krishna Bisetty, Biocomposites, 2018
Aasim Majeed, Raoof Ahmad Najar, Shruti Chaudhary, Sapna Thakur, Amandeep Singh, Pankaj Bhardwaj
In tissue engineering, nature and properties of scaffolds for cell attachment are crucial. Among the various scaffolds, electrospun fiber scaffolds mimic extracellular matrix and have greater surface-to-volume ratio to provide greater surface for attachment of cells. They find their application in neural, cardiovascular, musculoskeletal, and stem cell tissue engineering. A composite can be formed by encapsulating a protein into these fibers to provide additional properties. Peripheral nerve regeneration over large gaps is much difficult probably due to the formation of insufficient extracellular matrix [37] and lack of neurotrophic signals from distal nerve end [38]. The treatment involves grafting, which is limited by donor nerve availability. Use of synthetic nerve is another choice; however, it is successful only over small gaps. However, if the gap can be filled by extracellular matrix and neurotrophic signal is incorporated, the degree of success can be enhanced. Human glial cell-derived neurotrophic factor (GDNF) is a potent neurotrophic signal that promotes nerve fiber myelination and Schwann cell proliferation [39]. GNDF protein when encapsulated in the matrix of a biodegradable fiber of caprolactone and ethyl ethylene phosphate (PCLEEP) generates an aligned protein-polymer composite, which shows sustained release of GNDF up to a few months in rats having peripheral nerve injury. Protein-encapsulated fiber offered synergistic in vivo peripheral nerve regeneration ability to the composite, so it is well suited for in vivo tissue engineering experiments [40]. Similar encapsulation of human beta-nerve growth factor (NGF) in PCLEEP electrospun fibers showed sustained release of the protein up to three months, thereby confirming its use as a scaffold in tissue engineering [41].
Applications and hazards associated with carbon nanotubes in biomedical sciences
Published in Inorganic and Nano-Metal Chemistry, 2020
Ali Hassan, Afraz Saeed, Samia Afzal, Muhammad Shahid, Iram Amin, Muhammad Idrees
GDNF also stimulates the C18-4 cells. The assessment was made that if the silver nanoparticles (AgNPs) affected the GDNF-Src pathway or not. When AgNPs were used, it was proved that they were not binding to the GDNF or its receptors and further blocking the GDNF-Src pathway instead they bonded to the Fyn protein. The Fyn protein is a prevalent Src kinase protein found in the C180-4cells. The Fyn protein expression itself remains undisturbed however affects the downstream signaling cascade. The Fyn then inhibits the expression of N-Myc by disturbing the AKT signaling which in turn affects the SSC populations.[75]
Spinal dura mater: biophysical characteristics relevant to medical device development
Published in Journal of Medical Engineering & Technology, 2018
Sean J. Nagel, Chandan G. Reddy, Leonardo A. Frizon, Matthieu K. Chardon, Marshall Holland, Andre G. Machado, George T. Gillies, Matthew A. Howard, Saul Wilson
Polymeric nanofibers, also under study as dural substitutes, offer several advantages over existing artificial repair substrates [45]. The nanofiber scaffold can be coated with various proteins such as glial-derived neurotrophic factors (GDNF) that are slowly released. Early testing has shown that progenitor cells seeded onto the scaffold will differentiate into neurons.
Inhalation of polycarbonate emissions generated during 3D printing processes affects neuroendocrine function in male rats
Published in Journal of Toxicology and Environmental Health, Part A, 2023
Kristine Krajnak, Mariana Farcas, Walter McKinney, Stacey Waugh, Kyle Mandler, Alycia Knepp, Mark Jackson, Diana Richardson, MaryAnne Hammer, Joanna Matheson, Treye Thomas, Yong Qian
It is like that there was accumulation of PM in the nose in this study. It is possible that PM in the olfactory system either chemically or physically interfered with transmission of olfactory cues. Olfactory cues are needed to maintain both reproductive and metabolic function (Dintica et al. 2019; Lumia, Zebrowski, and McGinnis 1987; Kendrick et al. 1997). The mechanism by which inhaled fume components affect central nervous system function is not clear. 3DP emissions may impact the nervous system by directly entering the brain through the nose and olfactory system (Hubbs et al. 2011), or by altering olfactory input to regions of the brain that utilize olfactory information to regulate certain functions. For example, blocking olfactory input inhibits reproductive function (Lumia, Zebrowski, and McGinnis 1987; Powers and Winnans 1973). In the current study, it was found that inhalation of 3DP emissions resulted in a reduction in Mitotracker staining in the olfactory bulb after 1, 8 and 30 day exposure. The reduction in staining is indicative of a decrease in the number of active mitochondria in cells within the olfactory bulb (Buckman et al. 2001; Krajnak 2020; Kudryavtseva et al. 2016; Yu et al. 2016). A change in the number of active cells or in cell function might result in a reduction in olfactory signaling to the brain (Esposti et al. 1999; Kasahara and Scorrano 2014; Kudryavtseva et al. 2016). This alteration in active mitochondria in the olfactory bulb may be attributed to inhalation of PM, or to the estrogenic effects of BPA on mitochondrial function in exposed cells (Yager and Chen 2007). The decrease in Mitotracker staining was also accompanied by a reduction in GDNF and myelin basic protein (MBP) staining. GDNF was shown to be co-localized in myelinating glia Schwann cells and ensheathing cells in the olfactory bulb (Dintica et al. 2019; Kucera et al. 2019; Woodhall, West, and Chuah 2001). As mentioned above, a reduction in myelination of cells that project from the olfactory bulb to the brain may lead to decrease in the transmission of olfactory information and alterations in the transduction of cues that modulate reproductive and metabolic physiology (Baroncini et al. 2007; Lumia, Zebrowski, and McGinnis 1987; Mackay and Abidzaid 2018).