Abstract:
:Neurodegenerative diseases are associated with neuronal inclusions, comprised of protein aggregates. In Alzheimer's Disease (AD) and Lewy Body Disease (LBD) such lesions are distributed in a hierarchical retrograde transynaptic spatial pattern. This implies a retrograde transynaptic temporal propagation as well. There can be few explanations for this other than infectious agents (prions and viruses). This suggests that AD and LBD (at least) may have infectious origins. Transynaptic infiltration of the CNS along cranial nerve or other major projections, by one or more infectious agents has important implications. The clinical syndrome and natural history of each neurodegenerative disorder will reflect its portal of entry. There may be a different neurodegenerative syndrome for each cranial nerve or other portal of entry, and not all may manifest as "dementia". Each syndrome may be associated with more than one pathological lesion. Each pathology may be associated with several clinical syndromes. Host-parasite interactions are species specific. This may explain the rarity of AD-like pathology in most other older mammals. Over evolutionary timescales, the human brain should be adapted to predation by neurotropic agents. Viewed from this perspective, the prion-like pro-inflammatory and pro-apoptotic properties of β-amyloid and other proteins may be adaptive, and anti-microbial. Reductions in synaptic density may slow the progress of invading pathogens, while perineuronal nets and other structures may guard the gates. This suggests a defense in depth of a structure, the brain, that is inherently vulnerable to invasion along its neural networks.
journal_name
Med Hypothesesjournal_title
Medical hypothesesauthors
Royall DRdoi
10.1016/j.mehy.2012.11.005subject
Has Abstractpub_date
2013-02-01 00:00:00pages
118-21issue
2eissn
0306-9877issn
1532-2777pii
S0306-9877(12)00486-0journal_volume
80pub_type
杂志文章abstract::Oxidative stress plays a crucial role in a variety of clinical settings of atherogenesis, and mediates many pathways linked to atherosclerosis and inflammation. gamma-Glutamyltransferase (GGT), an enzyme responsible for the extracellular catabolism of antioxidant glutathione, may directly take part in atherogenesis an...
journal_title:Medical hypotheses
pub_type: 杂志文章,评审
doi:10.1016/j.mehy.2006.04.010
更新日期:2006-01-01 00:00:00
abstract::Sudden infant death syndrome (SIDS) is frequently associated with a mild infection, the incidence peaking during the third month of life. We hypothesize that the neonatal immaturity of both the acute febrile response and hypothalamus promote neonatal protection from SIDS. Vagal afferents modify the febrile response. V...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1054/mehy.1997.0695
更新日期:1999-06-01 00:00:00
abstract::Cannabinoid hyperemesis syndrome (CHS), a variant of cyclic vomiting syndrome, is an enigmatic and challenging clinical disorder. As cannabis legalization, use, and potency has increased worldwide over the past decade, so has the prevalence of CHS. These patients often require acute care and inpatient treatment for re...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2017.04.018
更新日期:2017-06-01 00:00:00
abstract::Antidepressants, including tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors and serotonin-noradrenalin reuptake inhibitors, are the main biological treatment for major depression. However, not all depressed patients improve clinically despite appropriate treatment. Thus,...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2005.10.011
更新日期:2006-01-01 00:00:00
abstract::Interleukin (IL)-17 is a pro-inflammatory cytokine originally described in T lymphocytes. Increased production of IL-17 has been linked to the induction of cytokines, chemokines and adhesion molecules in various cell types, effects that likely contribute to a number of inflammatory diseases including rheumatoid arthri...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2004.03.009
更新日期:2004-01-01 00:00:00
abstract::Schizophrenia, if not the most difficult, is one of the most difficult mysterious puzzles for psychiatrists, psychologists, and neuroscientists to solve. In this paper, based on the previously known pathologies of schizophrenia, a new model is proposed for explanation of the formation of positive psychotic symptoms of...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2006.03.054
更新日期:2006-01-01 00:00:00
abstract::Tubulointerstitial fibrosis is a final common pathway to the eventual structural desolation of kidneys. However, the mechanism involved in this phenomenon is still poorly understood, and current therapies are ineffective or only marginally effective. Mast cell has a variety of physiological and pathological functions ...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2006.10.059
更新日期:2007-01-01 00:00:00
abstract::The hypothesis is put forward that coronary heart disease (CHD) arises from a chronic imbalance between anabolism and catabolism in the body, induced by the psychosocial environment and mediated through the central nervous system (CNS) and neuroendocrine system. Psychosocial demands increase periods of waking arousal ...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/0306-9877(83)90044-0
更新日期:1983-11-01 00:00:00
abstract::Melasma is an acquired disorder of pigmentation that presents with asymptomatic symmetric darkening of the face. The pathogenesis of this condition is multifactorial and influenced by several factors including female sex hormones, genetic predisposition and ultraviolet light exposure. The management of melasma is usua...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2017.01.020
更新日期:2017-04-01 00:00:00
abstract::A primary goal in antimicrobial drug design is to find molecules which inhibit key proteins in bacteria without affecting mammalian homologues. To this aim, structural differences between eukaryotic and prokaryotic enzyme proteins involved in life processes are widely exploited. The membrane-bound enzyme complex ATP s...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2014.05.004
更新日期:2014-08-01 00:00:00
abstract::Yawning is a stereotyped event that occurs in humans and animals from fish to mammals, but neither its mechanisms nor its functions are entirely known. Its widespread nature suggests that it has important physiological functions. It is associated with stretching of muscles in a large area, but the function of this str...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2007.06.027
更新日期:2008-01-01 00:00:00
abstract::Acute carbon monoxide (CO) poisoning causes the neurologic symptoms and brain lesions during both acute and delayed phase. We propose that catecholamine crises in globus pallidus and deep white matter are the key pathophysiological factors causing acute and delayed brain injuries respectively. Increased sympathetic ac...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2014.04.032
更新日期:2014-08-01 00:00:00
abstract::Most of the body iron is found within hemoglobin in red cells (the erythron), a smaller amount being distributed in other tissues such as muscles and in deposits. Iron homeostasis is a finely tuned process in which the most important regulators are probably the liver-derived hepcidin which blocks iron absorption and d...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2014.09.008
更新日期:2014-11-01 00:00:00
abstract::Sixty percent of cases of clinical depression are considered to be treatment-resistant depression (TRD). Magnesium-deficiency causes N-methyl-d-aspartate (NMDA) coupled calcium channels to be biased towards opening, causing neuronal injury and neurological dysfunction, which may appear to humans as major depression. O...
journal_title:Medical hypotheses
pub_type: 杂志文章,评审
doi:10.1016/j.mehy.2009.10.051
更新日期:2010-04-01 00:00:00
abstract::In observing the phenomenon of alterations of tumor cell phenotypes, one may envision a mechanism that induces the change in tumor cell characteristics and the appearance of metastasis. Schirrmacher (1) has suggested that the effect of the microenvironment on tumor cells influences the control of gene expression and t...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/0306-9877(81)90010-4
更新日期:1981-05-01 00:00:00
abstract::We tested the hypothesis that if SPECT/CT-detected volumes of active and inactive parts of brain tissue present correlation with the results of hyperbaric oxygen therapy (HBOT) of ischemic stroke, SPECT imaging may serve as a selective tool for post-stroke patients to indicate cases that may significantly benefit from...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2019.109510
更新日期:2020-03-01 00:00:00
abstract::Logic, a fundamental component of research in the exact sciences is often not applied in prominent fields of medical research. Investigation into the aetiopathogenesis of headache, vertigo, and fatigue--acknowledged as the commonest and amongst the most prominent and debilitating of symptoms known to mankind--may be s...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/0306-9877(90)90025-a
更新日期:1990-04-01 00:00:00
abstract::Contrast-induced nephropathy (CIN) is regarded as acute tubular necrosis resulting from the cytotoxicity of contrast media and the medullary hypoxia linking to the interplay of vasoconstriction and vasodilatation. Saline infusion may prevent CIN by inhibiting renin release and thus production of angiotensin II (ANG II...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2015.09.020
更新日期:2015-12-01 00:00:00
abstract::The data of literature are discordant about the role of mast cells in different types of neoplasms. In this paper the authors propose the hypothesis that tumor-associated mast cells may switch to different polarization states, conditioning the immunogenic capacities of the different neoplasms. Anti-inflammatory polari...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2019.109281
更新日期:2019-10-01 00:00:00
abstract::It has been shown previously that the precipitator hypothesis of causation is able to account for certain key features of the epidemiological evidence that conflict with initiator and promoter hypotheses. The precipitator hypothesis states that the carcinogenic risk depends linearly in the average rate of smoking at a...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/0306-9877(81)90145-6
更新日期:1981-12-01 00:00:00
abstract::Anemia of chronic disease (ACD) is a condition of decreased red cell mass secondary to some other chronic inflammatory condition. In ACD total body iron stores are normal, though serum iron is typically low secondary to iron sequestration by macrophages, and often iron supplementation is not an effective treatment for...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2005.01.036
更新日期:2005-01-01 00:00:00
abstract::Delivery of large DNA constructs is necessary for combinatorial, anti-aging gene therapy. However, this is hindered by the lack of a non-inflammatory vector with sufficient packaging space and the ability to effectively spread through tissue. It is possible that a mitochondrion, altered to be able to secrete therapeut...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2018.05.014
更新日期:2018-08-01 00:00:00
abstract::As a common cause of chronic pelvic pain, endometriosis affects 10% of women of reproductive age. The most popular strategy for treating endometriosis is pseudo-pregnancy therapy. However, the efficacy of common systemic pseudo-pregnancy therapy is significantly attenuated by poor compliance because of so many side ef...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2009.08.001
更新日期:2010-01-01 00:00:00
abstract::A wealth of research data points to increased oxidative stress as a key driver of the cardiac remodeling triggered by chronic pressure overload, loss of functional myocardial tissue, or atrial fibrillation. Oxidative stress is a mediator of the cardiomyocyte hypertrophy and apoptosis, the cardiac fibrosis, and the def...
journal_title:Medical hypotheses
pub_type: 杂志文章,评审
doi:10.1016/j.mehy.2009.12.025
更新日期:2010-08-01 00:00:00
abstract::Although all multicellular organisms undergo structural and functional deterioration with age, senescence is not a uniform process. Rather, each organism experiences a constellation of changes that reflect the heterogeneous effects of age on molecules, cells, organs and systems, an idiosyncratic pattern that we refer ...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2009.12.031
更新日期:2010-06-01 00:00:00
abstract::Immune panels of many autism-spectrum children reveal signs of atypical infections and shifted cell counts. In conjunction with trait-related cerebral hypometabolism and hypoperfusion, these findings suggest a hypothesis: Several autism-spectrum subgroups derive from intra-monocyte pathogens such as measles virus, cyt...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1054/mehy.2000.1247
更新日期:2001-04-01 00:00:00
abstract::Superficial fraying, splitting and fibrillation of articular cartilage as a consequence of ageing or mechanical injury is not always associated with joint pain. However, similar cartilage lesions accompanied by synovitis and engorgement of the subchondral vasculature generally is; the disorder being known as osteoarth...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/0306-9877(93)90068-2
更新日期:1993-08-01 00:00:00
abstract::ATP sensitive (K(+)(ATP)) potassium cardiac channels are recruited when ATP levels are low as in ischemic injury and acute trauma. Such activation results in ECG-ST elevation and cardiac arrhythmias. K(+)(ATP) channel recruitment may be blocked by the sulfonylurea glibenclamide, permitting a wide variety of animal exp...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/s0306-9877(03)00055-0
更新日期:2003-04-01 00:00:00
abstract:UNLABELLED:Teeth start as bi-layered epithelial soft tissue follicles within bony jaws. Follicles grow into teeth and erupt. Early third molar follicles are detectable 8-9 years (±9 months). Intra-oral dental arches of jaws have finite space accommodating formed crowns. The last teeth to erupt are third molars. When th...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2012.05.031
更新日期:2012-09-01 00:00:00
abstract::For more than 35 years the author has treated multiple serious diseases in cats and dogs by correcting an unrecognized endocrine-immune imbalance originating with a deficiency or defect of cortisol. The cortisol abnormality creates a domino effect on feedback loops involving the hypothalamus-pituitary-adrenal axis. In...
journal_title:Medical hypotheses
pub_type: 杂志文章
doi:10.1016/j.mehy.2003.12.005
更新日期:2004-01-01 00:00:00