Minosykliini auttaa neurodegeneratiivisien sairauksien hoidossa:

A Novel Target of Action of Minocycline in NGF-Induced Neurite Outgrowth in PC12 Cells: Translation Initiation Factor eIF4AI

Kenji Hashimoto*, Tamaki Ishima

Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba, Japan

Abstract
Background

Minocycline, a second-generation tetracycline antibiotic, has potential activity for the treatment of several neurodegenerative and psychiatric disorders. However, its mechanisms of action remain to be determined.

Methodology/Principal Findings
We found that minocycline, but not tetracycline, significantly potentiated nerve growth factor (NGF)-induced neurite outgrowth in PC12 cells, in a concentration dependent manner. Furthermore, we found that the endoplasmic reticulum protein inositol 1,4,5-triphosphate (IP3) receptors and several common signaling molecules (PLC-γ, PI3K, Akt, p38 MAPK, c-Jun N-terminal kinase (JNK), mammalian target of rapamycin (mTOR), and Ras/Raf/ERK/MAPK pathways) might be involved in the active mechanism of minocycline. Moreover, we found that a marked increase of the eukaryotic translation initiation factor eIF4AI protein by minocycline, but not tetracycline, might be involved in the active mechanism for NGF-induced neurite outgrowth.

Conclusions/Significance
These findings suggest that eIF4AI might play a role in the novel mechanism of minocycline. Therefore, agents that can increase eIF4AI protein would be novel therapeutic drugs for certain neurodegenerative and psychiatric diseases.

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0015430

Lyme Disease Pathology - Central Nervous System
http://lymediseaseguide.org/lyme-disease-pathology-central-nervous-system

The spread of the Lyme disease bacteria into the central nervous system varies in incidence and speed between individuals but when it does happen the spirochaetes may fundamentally alter brain function. It appears that astrocytes in the brain are involved in the pathogenesis of Lyme disease as these are glial cells providing support for endothelial cells that constitute the blood-brain barrier that protects the brain from damage by closely guarding entrance to brain circulation. The astrocytes are also important in maintaining nutrient supply to brain tissue, and in the repair process, and scarring, following trauma to the spinal cord or brain itself. The Borrelia bacteria induce astrogliosis in the astrocytes, a process where the cells rapidly reproduce and then die (proliferation followed by apoptosis). The effectiveness of the blood-brain barrier, the supply of nutrients to neural tissue, and the balance of ions in the brain can all be compromised through such events.

Mielenkiintoista on astrosyyttien tuhoutuminen ja sitä kautta veriaivoesteen murtuminen ja ravinteiden pääseminen hermokudokseen. Zambonin mielestä veriaivoesteen läpäisykyky muuttui ja aivoihin pääsi ylimääräistä rautaa veren mukana.  Muistaakseni myös Prof. Thibault puhui astrosyyttien massakuolemasta syynä veriaivoesteen murenemiselle.

Our self-cleansing brain
Fluids coursing through the nervous system could help clear the brain of toxic detritus that leads to Alzheimer's

http://www.salon.com/2012/08/16/brains_drain_neuroscientists_discover_cranial_cl...

The brain can be a messy place. Thankfully, it has good plumbing: Scientists have just discovered a cleansing river inside the brain, a fluid stream that might be enlisted to flush away the buildup of proteins associated with Alzheimer’s, Huntington’s and other neurodegenerative disorders.

Scientific American The researchers, based at the University of Rochester (U.R.), University of Oslo and Stony Brook University, describe this new system in the journal Science Translational Medicine today. The study adds to the evidence that the star-shaped cells called astrocytes play a leading role in keeping the nervous system in good working order...The researchers observed that, like a river, cerebrospinal fluid carried these molecules rapidly along specific channels. Glial cells along the outside of arteries form these channels, creating a flume for cerebrospinal fluid that follows the brain’s blood vessels. In addition, the researchers found that these glial cells mediate the channel’s activity, assisting the flow of fluid through the channel.

From channels alongside arteries, the tracer-bearing fluid then passes through brain tissues. At the other end of tissues, it flows into similar channels along veins. The fluid follows these veins then either returns to the subarachnoid space, enters the bloodstream or eventually drains into the body’s lymphatic system. The researchers christened the network the “glymphatic” system, a nod to both glial cells and its functional similarity to the lymphatic system.

Iliff hypothesizes that a faulty glymphatic system may bear the blame for the over-accumulation of proteins seen in Alzheimer’s, amyotrophic lateral sclerosis, Huntington’s and other neurodegenerative disorders—and further study may even reveal a way to dispose of these clumps.

tuli vastaan duodecimin juttu vuodelta 2009

http://www.duodecimlehti.fi/web/guest/arkisto?p_p_id=dlehtihaku_view_article_WAR...

siinä Perttu J. Lindsberg, Jari Koistinaho ja Pentti Tienari
spekuloivat minosykliinillä ja MS:llä ihan mielenkiintoisella tavalla, myös hintanäkökulma tulee mukaan..

Kun tarpeeksi kauan odottaa, asiat tulevat uudelleen muotiin. Ja samoista asioista keksustellaan näköjään edelleen. Sääli, ettei lupaava lääke saa rahoitusta lisätutkimuksiin. CCSVI Facebookissa on myös keskustelua minosykliinistä.  Näköjään kannattaa ostaa ulkomailta ja tuoda mukanaan. Näin lomailu saa uuden ulottuvuuden..

Kilpikonnax, tuon facebookin kanssa no problem - teet vain feikki identiteetin ja haet sillä jäsenyyttä. Siellä on käsittääkseni muutamia mäsiä feikkinimillä ja ihan ok. Minosykliinistä ja muutamasta muusta antibiootista on siellä käyty keskusteluja ja ihmiset ovat niitä hankkineet joko ulkomailta tai erityislupahakemuksen myötä Suomesta.

Lisää edelliseen:

http://www.lymenet.de/literatur/brorson2001.htm

...Cysts were significantly associated with MS patients using each of the three different methods. This multi-method approach strengthens the association between CSF cysts and MS in a well-defined coastal area of southern Norway.  There are two possible explanations for the association between MS and CSF cysts: the cystic structures are either the agents causing MS or they have appeared in the CSF as a consequence of MS.

  The positive reaction with antispirochetal antiserum, the similarity of the cystic structures with cystic forms of spirochetes and the similarities between the cysts in the erythema migrans patient and the MS patients suggest that the patients were infected with a spirochete.  The  appearance of rod-like,slightly curved bacteria and spirochetes after culturing two of the CSF samples in BSK-H medium suggests the same.  Spirochetes may vary in appearance and may sometimes emerge as rod-like structures [18].  The fact that only two spinal fluids gave rise to  spirochete-like structures after culturing may be caused by the fact that cystic forms of spirochetes may often be difficult to convert to normal bacteria {11) and the BSK-H medium is not necessarily optimal for this possible unknown spirochete.

  It could be argued that the damage which MS caused in the brains of the patients had made them more vulnerable to spirochetal infection. But this does not seem a probable explanation. since all the MS patients had these cystic structures in their CFS. Other researchers have proposed that spirochetes could be the agents responsible for MS [5, 6, 8, 9]. For instance. Steiner [6] found spirochetes and granular bodies in brain autopsies of MS patients. These were proposed to belong to the genus BorreIia and were named Spirochaeta myelophthora [6].

  We previously studied spirochetes (B. burgdorferi) that have converted from spirochetes to cystic forms in CSF in vitro using the same methods as mentioned above [11].  With all these methods used in this study (TEM, AO, DF), the cystic structures observed in the CSF of the MS patients are morphologically similar to cystic forms of spirochetes. We found that cysts which are produced by inoculating  B. burgdorferi in CSF at 37  C can be PCR negative using conventional DNA extraction and OspA primers (unpublished observation). This is either because the cyst wall inhibits the entrance to the genome or because the genomes of spirochetes have been changed. We have also to keep in mind that PCR detection of B. burgdorferi spirochetes often may give false-negative  results [19).

  The positive IgG index associated with MS in our patient cohort proves that the patients had an active inflammatory process in the CNS (Table 1).  Inflammatory processes in the b~ and spinal cord of virtually any cause are usually less intense than inflammation in peripheral tissues and some microbiological agents, including spirochetes, provoke a very gentle inflammatory response [20, 21 ]. Considering the nature of MS, this disease could very well be a chronic infection and the clinical picture of MS has repeatedly been confused with neuroborreliosis [22-26). Therefore, we have both microbiological and some clinical support for the hypothesis that the cystic structures found in the CSF of the MS patients may originate from spirochetes which could be the causative agents of MS.


1930-luvulta aina toiseen maailmasotaan tutkittiin spirokeetta-teoriaa, mutta se lopahti tutkijoiden kuoltua. Vain Steiner jatkoi ja löysi borrelia- sukuun kuuluvan spirokeetan, jonka nimesi Spirochaeta myelophthoraksi. Kun muut eivät onnistuneet löytämään samaa bakteeria, tutkimus lopahti. Sanottakoon sen verran, että vaikka borrelioosin oireet on kirjattu jo 1880-luvulla, sen aiheuttava bakteeri löydettiin vasta 1970-luvulla.