Showing posts with label C.Neoformans. Show all posts
Showing posts with label C.Neoformans. Show all posts
Alzheimer’s disease: APP, gamma secretase, APOE, CLU, CR1, PICALM, ABCA7, BIN1, CD2AP, CD33, EPHA1, MS4A2, herpes simplex, C.pneumoniae and immunity
The major susceptibility genes identified in Alzheimer’s disease genome-wide association studies (APOE, ABCA7, BIN1, CLU, CD2AP, CD33, CR1, EPHA1, MS4A2 and PICALM), as well as APP and gamma-secretase are involved in the herpes simplex life cycle, or in that of other suspect pathogens (C.Pneumoniae, H.Pylori, C.Neoformans, B. Burgdorferri and P.Gingivalis) or in immune defence. As several of these pathogens can promote beta-amyloid deposition and tau phosphorylation in non-transgenic models, they might be considered as causative agents in the human condition, whose effects are tempered by susceptibility genes. Beta-amyloid is an antimicrobial peptide, and APP and gamma-secretase are highly expressed in dendritic cells, the scouts that present pathogen antigens to immunocompetent cells. Gamma secretase cleaves 21 viral or microbial receptors, including those for the suspect pathogens and the primary role of the amyloid/secretase network may well be related to pathogen disposal, effects which may be abrogated by the presence of beta-amyloid autoantibodies in the elderly. These autoantibodies, as well as those to nerve growth factor and tau, also observed in Alzheimer’s disease, may well in fact be antibodies to pathogens, as there exists a marked homology between the human autoantigens and pathogen proteins. Antibodies to NGF or tau promote beta-amyloid deposition, neurofibrillary tangles or cholinergic neuronal loss, and, with other autoantibodies, such as anti-ATPase, they are potential agents of destruction, whose formation is dictated by sequence homology between pathogen and human proteins, and thus by pathogen strain and human genes. The regular detection and elimination of pathogens in the ageing population might impact significantly upon the incidence of Alzheimer’s disease, and the early selective removal of culpable autoantibodies might offer hope for a cure. Tweet
mBiosphere: Spotlight: Cryptococcus neoformans
C.Neoformans is of interest, among others, because of two case reports describing compete reversal of dementia folowing fungal eradication.
Alzheimer's genes and risk factors
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Alzheimer's genes and risk factors
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The Fox and the Rabbits—Environmental Variables and Population Genetics (1) Replication Problems in Association Studies and the Untapped Power of GWAS (2) Vitamin A Deficiency, Herpes Simplex Reactivation and Other Causes of Alzheimer's Disease
Classical population genetics shows that varying permutations of genes and risk factors permit or disallow the effects of causative agents, depending on circumstance. For example, genes and environment determine whether a fox kills black or white rabbits on snow or black ash covered islands. Risk promoting effects are different on each island, but obscured by meta-analysis or GWAS data from both islands, unless partitioned by different contributory factors. In Alzheimer's disease, the foxes appear to be herpes, borrelia or chlamydial infection, hypercholesterolemia, hyperhomocysteinaemia, diabetes, cerebral hypoperfusion, oestrogen depletion, or vitamin A deficiency, all of which promote beta-amyloid deposition in animal models—without the aid of gene variants. All relate to risk factors and subsets of susceptibility genes, which condition their effects. All are less prevalent in convents, where nuns appear less susceptible to the ravages of ageing. Antagonism of the antimicrobial properties of beta-amyloid by Abeta autoantibodies in the ageing population, likely generated by antibodies raised to beta-amyloid/pathogen protein homologues, may play a role in this scenario. These agents are treatable by diet and drugs, vitamin supplementation, pathogen detection and elimination, and autoantibody removal, although again, the beneficial effects of individual treatments may be tempered by genes and environment.
Five-year survival after Helicobacter pylori eradication in Alzheimer disease patients.
This study showd that Helicobacter pylori eradication, while not curing Alzheimer's disease , has significant effecs on the mini-mental state examination score and prolonged patient life. Pathogens clearly contribute to Alzheimer's disease and the eradication of this and others, particularly herpes simplex Ref and Cryptococcus Neoformans Refs could significantly impact on the disease.
The human genome is composed of viral DNA
Evidence from over 2 million viral/human alignments, shows that the human genome is composed of viral DNA.
This is not just retroviruses (XMRV and HIV-1) but common viruses such as the rhinovirus, Epstein-Barr, influenza, herpes, papillomavirus, coronavirus and many more. This supports the idea, proposed over a century ago, by J.B.S.Haldane and Felix D'Herelle that viruses are responsible for the origin of life, and also the idea that viral inserts are responsible for evolutionary jumps.(the insertion of several viral genes, if passed on through the germ line, effectively creates a new being)
As if that were not interesting enough, here is the important factor , exemplified by Alzheimer's disease Bipolar disorder and schizophrenia. The insertion points of the viruses implicated as risk factors in any particular disease correspond to the locations of the genes implicated in the disease.
The more important the gene in Alzheimer's disease (and others), the more viral proteins it matches (and those of other pathogens).
These viral matches appear to cover the whole human genome, and every human protein is homologous to one virus or another.
In the human genome, these matches are characterised by millions of gapped consecutive and contiguous segments which translate into short contiguous peptide stretches (5-12 amino acids long).The older the viral insertion, the more fragmented the DNA, the shorter the protein matches,but the greater the number of human/viral homologues.
These human protein matches (vatches) are identical to those in the proteins expressed by the viruses implicated in the disease.
Because the viral protein is similar to human receptors, peptide ligands, enzymes, etc it can act as a dummy ligand or a decoy receptor, and also interfere with the interactome of its human counterpart. This is shown quite clearly in the DISC1/viral interactome
Upon infection, antibodies to the virus also risk targeting their human counterparts, which will in effect be knocked down when the antibody binds. The protein equivalent of gene knockouts. If the peptides are highly immunogenic, then cells containing the virus, or its human analogue will be targeted for destruction. This is exemplified by the fact that immunisation with tau in mice provokes the neurofibrillary tangle pathology seen in Alzheimer's disease.Tau is homologous to Herpes simplex and other viral proteins.
All of the diseases on the website pages Alzheimer's disease, Bipolar disorder, Schizophrenia, Chonic fatigue, and more, have an autoimmune component, pathogens are implicated in all, and the genes and pathogens fit together, hand in glove, for all (Bipolar disorder, Alzheimer's and schizophrenia).
Viruses (known and unsuspected culrits) are also homologous to the autoantigens in multiple sclerosis and to the mutant proteins in Huntington's disease and cystic fibrosis (see website)
This suggests that many human diseases work via this common mechanism, and therefore that most are preventable, by vaccination or elimination of the pathogen, and perhaps curable by immunosuppressant therapy.
Examples of how this works are here
A pdf of a prepublication is available at NaturePrecedings.
This is not just retroviruses (XMRV and HIV-1) but common viruses such as the rhinovirus, Epstein-Barr, influenza, herpes, papillomavirus, coronavirus and many more. This supports the idea, proposed over a century ago, by J.B.S.Haldane and Felix D'Herelle that viruses are responsible for the origin of life, and also the idea that viral inserts are responsible for evolutionary jumps.(the insertion of several viral genes, if passed on through the germ line, effectively creates a new being)
As if that were not interesting enough, here is the important factor , exemplified by Alzheimer's disease Bipolar disorder and schizophrenia. The insertion points of the viruses implicated as risk factors in any particular disease correspond to the locations of the genes implicated in the disease.
The more important the gene in Alzheimer's disease (and others), the more viral proteins it matches (and those of other pathogens).
These viral matches appear to cover the whole human genome, and every human protein is homologous to one virus or another.
In the human genome, these matches are characterised by millions of gapped consecutive and contiguous segments which translate into short contiguous peptide stretches (5-12 amino acids long).The older the viral insertion, the more fragmented the DNA, the shorter the protein matches,but the greater the number of human/viral homologues.
These human protein matches (vatches) are identical to those in the proteins expressed by the viruses implicated in the disease.
Because the viral protein is similar to human receptors, peptide ligands, enzymes, etc it can act as a dummy ligand or a decoy receptor, and also interfere with the interactome of its human counterpart. This is shown quite clearly in the DISC1/viral interactome
Upon infection, antibodies to the virus also risk targeting their human counterparts, which will in effect be knocked down when the antibody binds. The protein equivalent of gene knockouts. If the peptides are highly immunogenic, then cells containing the virus, or its human analogue will be targeted for destruction. This is exemplified by the fact that immunisation with tau in mice provokes the neurofibrillary tangle pathology seen in Alzheimer's disease.Tau is homologous to Herpes simplex and other viral proteins.
All of the diseases on the website pages Alzheimer's disease, Bipolar disorder, Schizophrenia, Chonic fatigue, and more, have an autoimmune component, pathogens are implicated in all, and the genes and pathogens fit together, hand in glove, for all (Bipolar disorder, Alzheimer's and schizophrenia).
Viruses (known and unsuspected culrits) are also homologous to the autoantigens in multiple sclerosis and to the mutant proteins in Huntington's disease and cystic fibrosis (see website)
This suggests that many human diseases work via this common mechanism, and therefore that most are preventable, by vaccination or elimination of the pathogen, and perhaps curable by immunosuppressant therapy.
Examples of how this works are here
A pdf of a prepublication is available at NaturePrecedings.
Familial and late-onset Alzheimer's disease: Autoimmune disorders triggered by viral, microbial and allergen mimics of beta-amyloid and APP mutants ?
Beta-amyloid (Aβ) autoantibodies are common in Alzheimer’s disease. Some may be derived from Herpes simplex and from 68 other phages and viruses expressing proteins that exactly match an immunogenic and fibrillogenic VGGVV Aβ sequence.Many other viral, microbial and allergenic proteins (particularly from dust mites) align with Aβ as do proteins from Borrelia burgdoferi, C.Pneumoniae, H.Pylori or P.Gingivalis or S.Mutans that cause periodontitis and tooth loss which are associated with Alzheimer's disease C.Neoformans which has been associated with a rare but curable form of the disorder also expresses proteins with homology toAβ . Immune-related proteins are present in amyloid plaques and the complement membrane attack complex in neurones in Alzheimer’s disease brains. Alzheimer’s disease may thus be an autoimmune disorder triggered by pathogenic antigens homologous to Aβ, whose antibodies target and kill Aβ containing neurones, via immune activation and complement-related lysis. This scenario explains many epidemiological observations in Alzheimer’s disease, which is more common in women and Afro-Americans, as is HSV-2 seroprevalence; related to the number of pregnancies (exposure to childhood infections) and less severe in nuns (low exposure to sexually transmitted diseases). Atopy and autoimmune disorders are common in Alzheimer’s disease in accord with allergen homology to Aβ, and anti-inflammatory agents reduce Alzheimer’s disease risk. Cancer-causing viruses (papillomavirus, hepatitis B, Epstein-Barr) and plant viruses from Mediterranean diet components align with the Aβ sequence targeted by catalytic autoantibodies, perhaps explaining the inverse association of diet and cancer with Alzheimer’s disease. As a papillomavirus vaccine already exists, it may have a role to play in Alzheimer’s disease. This scenario is also relevant to familial Alzheimer’s disease. Mutant forms of APP717 and the Swedish mutant convert the surrounding peptide to matches with commensal bacteria (E.Coli, E. Faecalis, P.Gingivalis) and to viruses with very high seroprevalence (HHV-6, norovirus, influenza and the common cold). Late-onset and Familial Alzheimer’s disease may both be autoimmune disorders caused by diverse common pathogens and allergens homologous to Aβ or mutant APP fragments. Immunosuppressants, vaccination and pathogen elimination may be of benefit in both conditions.See Alzheimer's disease risk factors
Pubmed: Autoimmunity and Alzheimer's and Herpes
Pubmed: Autoimmunity and Alzheimer's and Herpes
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