Nerve growth factor infusion in the primate brain reduces lesion-induced cholinergic neuronal degeneration. An inflammatory and trophic disconnect biomarker profile revealed in Down syndrome plasma: relation to cognitive decline and longitudinal evaluation. 120(Suppl. No use, distribution or reproduction is permitted which does not comply with these terms. doi: 10.1016/0006-8993(83)90045-8, Sofroniew, M. V., Galletly, N. P., Isacson, O., and Svendsen, C. N. (1990). The information you enter will appear in your e-mail message and is not retained by Medical Xpress in any form. |, NGF is Responsible for the Maintenance of the Cholinergic Phenotype, Possible Clinical Application of Exogenous NGF, Atrophy of BFCNs in AD and its Causes and the NGF Paradox, A Novel NGF Metabolic Pathway and its Pharmacological Validation, The NGF Metabolic Pathway in AD and in DS With AD Pathology, Novel Developments Regarding the Implication of the Cholinergic System in AD, Creative Commons Attribution License (CC BY). Further to it, research on such trophic interactions could help identify novel biomarkers signaling a progressive preclinical AD pathology and pave the way for novel therapeutic interventions for AD and associated pathologies with NGF cholinergic involvement. 112, 161–173. The NGF pathway may also have potential as a biomarker of cognitive decline in AD, as its changes can predict future cognitive decline in patients with Down syndrome as they develop preclinical Alzheimer’s pathology. These processes are important for normal physiology, so it is not surprising that disease states result from major alterations in their function, but whether relatively minor perturbations of this metabolism contribute to neurodegeneration requires further study… N. Y. Acad. doi: 10.1111/j.1471-4159.2011.07507.x, Garofalo, L., and Cuello, A. This document is subject to copyright. Microdosing of scopolamine as a “cognitive stress test”: rationale and test of a very low dose in an at-risk cohort of older adults. 17, 8984–8996. doi: 10.1111/jphp.12919, Whitehouse, P. J., Price, D. L., Clark, A. W., Coyle, J. T., and DeLong, M. R. (1981). doi: 10.4088/JCP.15m10413, Cavedo, E., Grothe, M. J., Colliot, O., Lista, S., Chupin, M., Dormont, D., et al. 10, 3801–3813. 2), S111–S115. 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Basal forebrain volume, but not hippocampal volume, is a predictor of global cognitive decline in patients with Alzheimer’s disease treated with cholinesterase inhibitors. doi: 10.1001/jamaneurol.2015.1807, Venero, J., Knüsel, B., Beck, K., and Hefti, F. (1994). Cell Rep. 24, 38–46. Brain Res. Rep. 7:11706. doi: 10.1038/s41598-017-09780-3, Chuang, Y.-F., Elango, P., Gonzalez, C. E., and Thambisetty, M. (2017). Nerve growth factor gene expression in the developing rat brain. 289, 1000–1010. ACC, RP, and HH wrote and edited the manuscript. doi: 10.1002/ana.410100203, Whitehouse, P. J., Price, D. L., Struble, R. G., Clark, A. W., Coyle, J. T., and Delon, M. R. (1982). The PFC is highly involved in cognition, working memory, and decision making 2. A., Skau, K. A., and Crutcher, K. A. doi: 10.1016/0014-4886(91)90066-L, Koliatsos, V. E., Nauta, H., Clatterbuck, R. E., Holtzman, D. M., Mobley, W. C., and Price, D. L. (1990). Alzheimer’s Dementia 11, 1041–1049. In 1982, Whitehouse and collaborators proposed that the cortical cholinergic biochemical depletion in AD was due to the loss of magnocellular (presumed cholinergic) neurons of the nucleus basalis, based on Nissl studies in which only the large (magnocellular) neurons were counted (Whitehouse et al., 1982). Effects of nerve growth factor on the development of the dendritic system of cholinergic neurons in dissociated culture of the rat septum. New developments, such as the ones highlighted above, have led to a renewed interest regarding the neurobiology of the BF cholinergic system in health and in neurodegenerative conditions. Differential modulation of the cholinergic phenotype of the nucleus basalis magnocellularis neurons by applying NGF at the cell body or cortical terminal fields. Alzheimer’s Res. Regulation of enzyme synthesis, namely through the induction or repression of transcription. 68, 1309. doi: 10.1097/NEN.0b013e3181c22569, Burgos, I., Cuello, A. C., Liberini, P., Pioro, E., and Masliah, E. (1995). NGF-induction of the expression of ChAT mRNA in PC12 cells and primary cultures of embryonic rat basal forebrain. DS brains also exhibited elevated zymogenic activity of MMP9, thereby exacerbating the degradation of the limited amount of available biologically active mNGF (Iulita et al., 2014). Association between anticholinergic medication use and cognition, brain metabolism, and brain atrophy in cognitively normal older adults. 272, 527–545. At about the same time, in a TINS review, we raised the possibility that the cholinergic atrophy could be secondary to a cortical lesion in AD (Cuello and Sofroniew, 1984) and Bartus et al. Such goals await the development of biomarkers defining unequivocally a progressing AD pathology before its clinical presentation. Donepezil for dementia due to Alzheimer’s disease. Delayed treatment with nerve growth factor reverses the apparent loss of cholinergic neurons after acute brain damage. We found that released proNGF is converted to mNGF and ultimately degraded by metalloproteases in the extracellular space. (1991). JAMA Neurol. 24, 551–600. Covalent enzyme modification 4. 98, 265–265. J. Neurochem. Science 217, 408–414. Nerve growth factor in Alzheimer’s disease: increased levels throughout the brain coupled with declines in nucleus basalis. J. Neurosci. The Organization of Behavior: A Neuropsychological Theory. Neurobiol. Acad. doi: 10.1111/j.1471-4159.1985.tb05517.x, Takei, N., Tsukui, H., and Hatanaka, H. (1988). In AD, BF cholinergic neurons lose their cholinergic phenotype and function, suggesting an impairment in NGF-mediated trophic support. See more ideas about Biochemistry, Mcat study, Biology. Increased Matrix Metalloproteinase-9 activity in mild cognitive impairment. Dietary amino acids provide a large amount of carbon and nitrogen to the body that can be metabolized by a myriad of biochemical pathways. Enolase is an essential enzyme involved in glycolysis, a metabolic pathway that is elevated in many cancers to fuel their increased cell growth. 45, 1021–1026. In a further study, impaired proNGF cortical maturation following infusion of α2-antiplasmin was sufficient to alter BFCN phenotype. (2018). Brain Res. JAMA Neurol. Med. Tryptophan (Trp) is an essential amino acid in all animals, which is synthesized and provided to higher trophic levels by bacteria, fungi and plants.
We further validated this pathway by demonstrating that pharmacological inhibition of the maturation or degradation enzymatic pathway can trigger proNGF/mNGF imbalances (Allard et al., 2012, 2018). Neurosci. Mouse nerve growth factor prevents degeneration of axotomized basal forebrain cholinergic neurons in the monkey. This concept is frequently questioned by the fact that cholinergic therapy only provides modest and transient cognitive relief in AD. Rev. The NGF Metabolic Pathway in AD and in DS With AD Pathology. Metabolic regulation is a term used to describe the process by which metabolic pathways (both the anabolic/biosynthetic and catabolic/degradative pathways) are regulated in mammals. (1985) revised the status of “The Cholinergic Hypothesis,” clarifying further that “it states nothing about etiological factors” but rather describes the role of cholinergic dysfunction in memory mechanisms.
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