Alzheimer's and Dementia: Drugs to correct micro-tube defects promise to treat Alzheimer's disease.

The brain of Alzheimer's disease (AD) patients is characterized by extracellular aging plaques consisting of amyloid beta (A beta) peptides, as well as intracellular enveraged bodies formed by tau proteins, commonly known as nerve fiber tangles.
a beta peptide that forms plaques is produced by protein cutting of amyloid prebiotic proteins (APP) by beta APP cutting enzymes (BACE) and gamma-secretases.
studies have found that mutations in APP and the presenilin (PS) protein that make up the enzyme activity in the gamma-secretase complex lead to familial AD, which leads to the thesis of 'amyloid protein cascading'.
hypothesis assumes that the A-beta plaque initiates a series of events that lead to neuron loss and cognitive impairment in AD disease.
A beta aging plaques may promote AD neurodegeneration by promoting the spread of tau pathology in the brain from the initial endothys/hippoctic regions to the neo-cortical regions.
note that the extent of tau pathology, rather than the burden of aging plaques, is associated with AD cognitive state, which is consistent with tau pathology leading to AD neurodegeneration.
how aging plaques enhance the molecular mechanisms of tau pathology is largely unknown.
Tau is usually a micro-tube (MT)-related protein that is supposed to provide stable axon MTs in the far-end lip region, while also preventing MT from being cut off.
MTs play a vital role in neurons because they are the channel through which cell components extend along the axons through the axon transport process.
Tau becomes highly phosphate in AD, which promotes its departure from MTs and increases the dynamicity of MT, which may lead to MT breakage and damage to shaft transport.
combination of tau and MTs may also affect the interaction of molecular motors involved in axon transport.
As a result, the loss of tau's MT regulation function, as well as the formation of insoluble tau deposits, may lead to neuron loss observed in AD and related tau diseases such as Pick disease, peritic nuclear paralysis, and cortical substrate degeneration.
the above phenomenon, it can be inferred that the brain permeable MT stabilization compound can normalize MT and axon transport in the mouse model of tau pathology, thereby reducing neuron loss and tau pathology.
MT dysfunction was also observed in atrophy axons adjacent to the A-beta plaque, leading to the accumulation of amyloid pregenital proteins (APP) and BACE1, and possibly enhancing the production of local A-beta.
recently, researchers wrote a paper in Alzheimer's and Dementia to examine whether the brain-penetrating MT stabilizer CNDR-51657 can reduce plaque-related axon atrophy and release of A-beta.
the model it uses is a 5XFAD mouse that can form rich A-beta plaques.
researchers assolution of CNDR-51657 to 1.5-month-old male and female 5XFAD mice found that continuous dosage for 4 or 7 weeks reduced the amount of soluble brain A beta, consistent with lower app and BACE1 levels, and further led to a decrease in insoluble A-beta deposits.
data indicate a vicious circle in which the formation of the initial A-beta plaque causes MT damage in the nearby axons, leading to local accumulation of APP and BACE1, facilitating additional A-beta production and plaque deposition.
MT stabilizer compounds can reduce this cycle and the damage caused by tau-MTs binding defects, suggesting that this type of molecule has the potential to become a potential AD therapy drug.
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