1.
Gut microbiota in dementia. Critical review of novel findings and their potential application.
Łuc, M, Misiak, B, Pawłowski, M, Stańczykiewicz, B, Zabłocka, A, Szcześniak, D, Pałęga, A, Rymaszewska, J
Progress in neuro-psychopharmacology & biological psychiatry. 2021;:110039
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Abstract
There is a great deal of impetus for the comprehensive understanding of the complete pathological function, genetic information, and functional diversity of the gut microbiota that favors the development of dementia. It has been reported that patients with mild cognitive impairment and Alzheimer's disease present with several metabolic and immune-inflammatory alterations. The recently highlighted aspects of human health linked to cognitive decline include insulin-resistance, obesity, and chronic low-grade inflammation. Gut microbiota is known to produce neurotransmitters, such as GABA, acetylcholine, dopamine or serotonin, vitamins, intestinal toxins, and modulate nerve signaling - with emphasis on the vagus nerve. Additionally, gut dysbiosis results in impaired synthesis of signaling proteins affecting metabolic processes relevant to the development of Alzheimer's disease. Due to numerous links of gut microbiota to crucial metabolic and inflammatory pathways, attempts aimed at correcting the gut microflora composition may affect dementia pathology in a pleiotropic manner. Taking advantage of the metabolic effects of cold exposure on organisms by the introduction of whole-body cryostimulation in dementia patients could lead to alterations in gut microbiota and, therefore, decrease of an inflammatory response and insulin resistance, which remain one of the critical metabolic features of dementia. Further studies are needed in order to explore the potential application of recent findings and ways of achieving the desired goals.
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Evaluation of the Neuroprotective Potential of N-Acetylcysteine for Prevention and Treatment of Cognitive Aging and Dementia.
Hara, Y, McKeehan, N, Dacks, PA, Fillit, HM
The journal of prevention of Alzheimer's disease. 2017;(3):201-206
Abstract
Alzheimer's disease is a progressive neurodegenerative disease for which there is no cure and only a few treatments providing little relief. Increased oxidative stress that is associated with aging is strongly implicated in the pathogenesis and progression of Alzheimer's disease. Studies have shown that levels of the endogenous antioxidant glutathione decline at an early stage of Alzheimer's disease with decreased levels correlating with worse cognitive functions. N-acetylcysteine, a drug also widely available as a dietary supplement, is a precursor of L-cysteine, which in turn is a component of glutathione. Because cysteine availability is a limiting factor for glutathione synthesis, treatment with N-acetylcysteine may increase glutathione levels and thereby counter oxidative stress, promote redox -regulated cell signaling, and improve immune responses. In this review, we evaluate the existing literature and the potential of N-acetylcysteine in promoting cognitive health and alleviating cognitive decline associated with dementia. Discussion will also include possible mechanisms of action of N-acetylcysteine, its effects on aging biology, and safety of long-term use. Based on the available literature, a nutraceutical formulation containing N-acetylcysteine among other compounds has shown some pro-cognitive benefits in Alzheimer's patients and older adults, but the evidence for N-acetylcysteine alone is less robust. Although N-acetylcysteine crosses the blood-brain-barrier, low bioavailability is an obstacle. One promising avenue of research may be to explore derivatives of N-acetylcysteine such as N-acetylcysteine amide, which has been reported in preclinical studies to have higher permeability through cellular and mitochondrial membranes with increased central nervous system bioavailability compared to N-acetylcysteine.
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TRPM7 and TRPM2-Candidate susceptibility genes for Western Pacific ALS and PD?
Hermosura, MC, Garruto, RM
Biochimica et biophysica acta. 2007;(8):822-35
Abstract
Recent findings implicating TRPM7 and TRPM2 in oxidative stress-induced neuronal death thrust these channels into the spotlight as possible therapeutic targets for neurodegenerative diseases. In this review, we describe how the functional properties of TRPM7 and TRPM2 are interconnected with calcium (Ca(2+)) and magnesium (Mg(2+)) homeostasis, oxidative stress, mitochondrial dysfunction, and immune mechanisms, all principal suspects in neurodegeneration. We focus our discussion on Western Pacific Amyotrophic Lateral Sclerosis (ALS) and Parkinsonism Dementia (PD) because extensive studies conducted over the years strongly suggest that these diseases are ideal candidates for a gene-environment model of etiology. The unique mineral environment identified in connection with Western Pacific ALS and PD, low Mg(2+) and Ca(2+), yet high in transition metals, creates a condition that could affect the proper function of these two channels.
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Homocysteine but not neopterin declines in demented patients on B vitamins.
Frick, B, Gruber, B, Schroecksnadel, K, Leblhuber, F, Fuchs, D
Journal of neural transmission (Vienna, Austria : 1996). 2006;(11):1815-9
Abstract
Inflammation and immune system activation seem to play an important role in the development and progression of dementia. Hyperhomocysteinemia is common in various forms of dementia, and a significant relationship was found between concentrations of homocysteine and immune activation marker neopterin. B vitamin supplementation is able to slow-down homocysteine formation in patients. In an open-label study, effects of B vitamin supplementation (Beneuran compositum ) on concentrations of homocysteine and neopterin were investigated in 58 patients with Alzheimer's disease (n=30), vascular dementia (n=12) and mild cognitive impairment (n=16). In all groups of patients, a significant percentage of patients presented with homocysteine concentrations >15 micromol/L and with elevated concentrations of immune activation marker neopterin. Decline of homocysteine concentrations was observed after one month of B vitamin supplementation (all p<0.01; paired Kruskal-Wallisn-test). By contrast, neopterin concentrations remained unchanged (all p>0.05). B vitamin supplementation in patients with various forms of dementia did not influence neopterin concentrations, which indicates that the degree of immune activation and inflammation remained unchanged. The question remains, if lowering of homocysteine by folate supplementation alone could have any beneficial effect to modulate the course of dementia development and if longer period of supplementation would also ameliorate immune system activation status.