From an article I found about opiates and taupathies. Related to Alzheimers, but wondered about PSP...could codeine/opiates cause PSP? Could minocycline be useful-has anyone tried it? (see end of article)
Excerpt below (link to full article at end)
What are the recent advances?
The new discoveries relate to abnormal proteins within the dendritic spines and their heads. These are the tau proteins and the proteins of the post-synaptic density.
What are tau proteins and how were they abnormal?
The dendritic spines have scaffold-like structures called microtubules within them in order to maintain their shape. Tau proteins help stabilise the microtubules. Abnormal tau proteins result in an abnormal immune response and reduction in dendritic spine density (dendritis or dendropathy) in the hippocampus or memory centre (hippocampitis) and Alzheimer`s disease.
The recent discovery was by Dezhi Liao, Ph.D. Associate Professor , Department of Neuroscience University of Minnesota who has previously challenged the conventional model of opioid dependency using a dendritic spine model. ( Mu-opioid receptors modulate the stability of dendritic spines) Associate Professor Liao found that tau protein accumulated in dendritic spines and led to abnormal synapses. These changes occurred prior to nerve cell death in Alzheimer`s disease.
What is the post-synaptic density (PSD) and how was it abnormal?
The PSD is a circular disc with a central depression i.e. doughnut shaped, which lies in the head of the dendritic spine. The disc lies below the synapses. There are abnormal mutations of the proteins of the PSD in many psychiatric and neurological diseases. These mutations are associated with an abnormal immune response within the brain and reduction in dendritic spine density (dendritis or dendropathy).
Professor Seth Grant and colleagues isolated 1461 proteins from the PSD. Mutations of PSD proteins caused 133 neurological and psychiatric diseases.
These findings provide further evidence that most psychiatric and neurological diseases may relate to the model of
1. An abnormal immune response to an immunogen or auto-immunogen.
2. Genetic predisposition.
3. Abnormal dendritic spines (dendritis/dendropathy).
4. Clinical features.
Dr Noble et al have used minocycline (an antibiotic) in mice with abnormal tau protein related Alzheimer`s disease. The minocycline was noted to reduce inflammatory markers which are elevated in Alzheimer`s disease. No mention was made of the effect on dendritic spinesor clinical features in the treated animals.
Minocycline has already been used in animals with fragile X syndrome and was noted to promote dendritic spine maturation perhaps by an anti-inflammatory action. Minocycline has been used in a small clinical trial in patients with fragile X syndrome with some success. Larger trials are awaited.
It is possible that suppression of the abnormal immune response to abnormal proteins may be important in the treatment of brain disease in the future.
Perhaps brain disease will soon be regarded as neuro-inflammatory rather than neuro-degenerative.
Characterization of the proteome, diseases and evolution of the human postsynaptic density
Alzheimer's: Tau Disrupts Neural Communication Prior to Neurodegeneration
Anti-inflammatory impact of minocycline in a mouse model of tauopathy
Minocycline promotes dendritic spine maturation and improves behavioural performance in the fragile X mouse model.