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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.
Amphiphilic Nanocarrier Systems for Curcumin Delivery in Neurodegenerative Disorders
Published in Shaker A. Mousa, Raj Bawa, Gerald F. Audette, The Road from Nanomedicine to Precision Medicine, 2020
Miora Rakotoarisoa, Angelina Angelova
Alzheimer’s disease (AD) is the most common cause of dementia. It currently affects about 10% of the world’s population over 60–65 years of age, and about 50% over 85 years of age. More than 30 million people may expect to be affected by AD during the next 20 years due to the increasing lifespan of the world population [1, 2]. Major pathological features of AD include the accumulation of extracellular amyloid plaques and fibrils, intracellular neurofibrillary tangles, and disruption of the cholinergic transmission, including reduced acetylcholine levels in the basal forebrain (Table 33.1). The most common symptom is the short-term memory loss, i.e., difficulty in remembering recent events [2–5]. Other symptoms include disorientation, mood, language, and behavioral issues, and loss of motivation, depending on the progression of the disease. The treatments of AD have employed acetylcholinesterase inhibitors (tacrine, rivastigmine, galantamine, and donepezil) to overcome the decrease of the ACh levels as a result of the death of cholinergic neurons. The NMDA receptor antagonist (memantine) acts by inhibiting the overstimulation by glutamate, which can cause cell death. Atypical antipsychotics have modest efficacy in reducing the aggression and psychosis of AD patients. These medications provide little benefit, and provoke various adverse effects [6, 7].
Amphiphilic Nanocarrier Systems for Curcumin Delivery in Neurodegenerative Disorders
Published in Shaker A. Mousa, Raj Bawa, Gerald F. Audette, The Road from Nanomedicine to Precision Medicine, 2019
Miora Rakotoarisoa, Angelina Angelova
Alzheimer’s disease (AD) is the most common cause of dementia. It currently affects about 10% of the world’s population over 60–65 years of age, and about 50% over 85 years of age. More than 30 million people may expect to be affected by AD during the next 20 years due to the increasing lifespan of the world population [1, 2]. Major pathological features of AD include the accumulation of extracellular amyloid plaques and fibrils, intracellular neurofibrillary tangles, and disruption of the cholinergic transmission, including reduced acetylcholine levels in the basal forebrain (Table 33.1). The most common symptom is the short-term memory loss, i.e., difficulty in remembering recent events [2–5]. Other symptoms include disorientation, mood, language, and behavioral issues, and loss of motivation, depending on the progression of the disease. The treatments of AD have employed acetylcholinesterase inhibitors (tacrine, rivastigmine, galantamine, and donepezil) to overcome the decrease of the ACh levels as a result of the death of cholinergic neurons. The NMDA receptor antagonist (memantine) acts by inhibiting the overstimulation by glutamate, which can cause cell death. Atypical antipsychotics have modest efficacy in reducing the aggression and psychosis of AD patients. These medications provide little benefit, and provoke various adverse effects [6, 7].
A novel solution of an elastic net regularisation for dementia knowledge discovery using deep learning
Published in Journal of Experimental & Theoretical Artificial Intelligence, 2023
Kshitiz Shrestha, Omar Hisham Alsadoon, Abeer Alsadoon, Tarik A. Rashid, Rasha S. Ali, P.W.C. Prasad, Oday D. Jerew
(W. Huang et al., 2018) enhanced a system to detect dementia disease using low-resource pairwise learning. The authors use a deep learning algorithm on Arterial Spin Labelling (ASL) magnetic resonance images. As future work, the model needs to work more on medical imaging problems using sophisticated deep learning techniques. (J. E. Lee et al., 2016) examines Nucleus basalis magno-cellularis stimulation to study the changes in spatial memory and neurotransmitter systems. The authors use 192 IgG-saporin for basal forebrain cholinergic neuron degeneration associated with memory and learning. The proposed system provides a piece of new information that consolidation and retrieves the visuospatial memory which is enhanced by Nucleus basalis magnocellularis stimulation. However, it is not clear how much the electrical stimulation effects and make changes in the neurotransmitter system, and they are related to visuospatial memory. The study of the electrical stimulation mechanism and the neurotransmitter systems will be considered as the future work of this paper. (H. Akinori et al., 2018) constructed a Multiple Layer Perceptron as a predictive model that predicts the outcome of the Morris Water Maze. The authors use the output data of the Morris Water Maze operation and fed it to the Artificial Neural Networks as an input. The output results of the Artificial Neural Network model and Morris Water Maze operation were compared. The prediction accuracy between the human tester and the Artificial Neural Network model is similar. Apart from that, the accuracy of the predictive model is affected when the explanatory and the objective variables are on the same data representation.