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      Production of the Acetylcholinesterase Inhibitor from Yarrowia lipolytica S-3

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          Abstract

          The acetylcholinesterase (AChE) inhibitor of Yarrowia lipolytica S-3 was maximally produced when it was incubated at 30℃ for 36 h in an optimal medium containing 1% yeast extract, 2% peptone and 2% glucose, with an initial pH 6.0. The final AChE inhibitory activity under these conditions was an IC 50 value of 64 mg/ ml. After partial purification of the AChE inhibitor by means of systematic solvent extraction, the final IC 50 value of the partially purified AChE inhibitor was 0.75 mg/ ml. We prepared a test product by using the partially purified AChE inhibitor and then determined its stability for the development of a new antidementia commercial product. The test product was stable at room temperature for 15 weeks.

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          Neuromodulation and cortical function: modeling the physiological basis of behavior.

          Michael E. Hasselmo (1995)
          Neuromodulators including acetylcholine, norepinephrine, serotonin, dopamine and a range of peptides alter the processing characteristics of cortical networks through effects on excitatory and inhibitory synaptic transmission, on the adaptation of cortical pyramidal cells, on membrane potential, on the rate of synaptic modification, and on other cortical parameters. Computational models of self-organization and associative memory function in cortical structures such as the hippocampus, piriform cortex and neocortex provide a theoretical framework in which the role of these neuromodulatory effects can be analyzed. Neuromodulators such as acetylcholine and norepinephrine appear to enhance the influence of synapses from afferent fibers arising outside the cortex relative to the synapses of intrinsic and association fibers arising from other cortical pyramidal cells. This provides a continuum between a predominant influence of external stimulation to a predominant influence of internal recall (extrinsic vs. intrinsic). Modulatory influence along this continuum may underlie effects described in terms of learning and memory, signal to noise ratio, and attention.
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            A molecular link between the active component of marijuana and Alzheimer's disease pathology.

            Lisa M Eubanks, Claude J Rogers, Albert E Beuscher … (2006)
            Alzheimer's disease is the leading cause of dementia among the elderly, and with the ever-increasing size of this population, cases of Alzheimer's disease are expected to triple over the next 50 years. Consequently, the development of treatments that slow or halt the disease progression have become imperative to both improve the quality of life for patients and reduce the health care costs attributable to Alzheimer's disease. Here, we demonstrate that the active component of marijuana, Delta9-tetrahydrocannabinol (THC), competitively inhibits the enzyme acetylcholinesterase (AChE) as well as prevents AChE-induced amyloid beta-peptide (Abeta) aggregation, the key pathological marker of Alzheimer's disease. Computational modeling of the THC-AChE interaction revealed that THC binds in the peripheral anionic site of AChE, the critical region involved in amyloidgenesis. Compared to currently approved drugs prescribed for the treatment of Alzheimer's disease, THC is a considerably superior inhibitor of Abeta aggregation, and this study provides a previously unrecognized molecular mechanism through which cannabinoid molecules may directly impact the progression of this debilitating disease.
            Article 0 comments Cited 71 times – based on 0 reviews     Review now
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              Cholinergic markers in elderly patients with early signs of Alzheimer disease.

              Petar D. Marin, Paula M Lantz, R C Mohs … (1999)
              A central tenet of Alzheimer disease (AD) is the loss of cortical cholinergic function and cholinergic markers in postmortem brain specimens. Whether these profound deficits in cholinergic markers found in end-stage patients are also found in patients with much earlier disease is not known. To determine whether cholinergic deficits in AD precede, follow, or occur in synchrony with the earliest signs of cognitive deterioration. Postmortem study of nursing home residents with Clinical Dementia Rating (CDR) Scale scores of 0.0 to 2.0 and 4.0 to 5.0 who underwent autopsy between 1986 and 1997, comparing the activity of the cholinergic marker enzymes in the cortices of 66 elderly subjects with no (CDR score = 0.0; n = 18), questionable (CDR score = 0.5; n = 11), mild (CDR score = 1.0; n = 22), or moderate (CDR score = 2.0; n = 15) dementia vs subjects with severe dementia (CDR score = 4.0-5.0; n = 15). Activity of the cholinergic marker enzymes choline acetyltransferase and acetylcholinesterase in 9 neocortical brain regions. The activity of choline acetyltransferase and acetylcholinesterase in 9 neocortical brain regions did not differ significantly in subjects with CDR scores of 0.0 to 2.0, but was significantly lower in subjects with severe dementia (CDR score = 4.0-5.0). Choline acetyltransferase levels were significantly correlated with severity of neuropathological lesions of AD, as measured by density of neuritic plaques and neurofibrillary tangles. Although neocortical cholinergic deficits are characteristic of severely demented AD patients, in this study, cholinergic deficits were not apparent in individuals with mild AD and were not present until relatively late in the course of the disease. These results suggest that patients with more severe disease should be a target for cholinergic treatment.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Mycobiology
                Journal ID (iso-abbrev): Mycobiology
                Journal ID (publisher-id): MB
                Title: Mycobiology
                Publisher: The Korean Society of Mycology
                ISSN (Print): 1229-8093
                ISSN (Electronic): 2092-9323
                Publication date (Print): June 2008
                Publication date (Electronic): 30 June 2008
                Volume: 36
                Issue: 2
                Pages: 102-105
                Affiliations
                [1 ]Department of Life Science and Genetic Engineering, Paichai University, Daejeon 302-735, Korea.
                [2 ]Korea Food Research Institute, Sungnam 463-746, Korea.
                Author notes
                Corresponding author ( biotech8@ 123456pcu.ac.kr )
                Article
                DOI: 10.4489/MYCO.2008.36.2.102
                PMC ID: 3755231
                PubMed ID: 23990742
                SO-VID: 6e21e316-0d5a-42eb-aa86-b53d1f8fd050
                Copyright © Copyright © 2008 The Korean Society of Mycology
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 04 April 2008
                Date accepted : 16 May 2008
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Plant science & Botany
                Keywords: yarrowia lipolytica s-3,antidementia,acetylcholinesterase inhibitor
                Data availability:
                ScienceOpen disciplines: Plant science & Botany
                Keywords: yarrowia lipolytica s-3, antidementia, acetylcholinesterase inhibitor

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