Gatekeepers.

We all know what that means if we are trying to reach a corporate executive, or trying to enter that wonderful nightclub.

But, there are more important gatekeepers in our lives.

There are protein complexes that bind with different compounds and, in so doing, affect the ability of nutrients, of vital components to cross in and out of the cells.

We think of cell membranes or nuclear membranes (aka envelope) as solid structures.  But, they aren’t.  They are replete with pores (holes).  Nuclear pore complexes penetrate these structures (double-membrane nuclear envelopes)- and are continuous with the endoplasmic reticulum (ER).  The ER is an organelle that harbors protein synthesis, lipid production, even toxin removal.   (You can consider the ER as a riverbed that affords a network to bring food to distant locations and remove trash from the cell.)

When those complexes are disrupted (from an improper flux of proteins), the cell manifests problems.  These failures have been linked with aging, ALS (amyotrophic lateral sclerosis, aka Lou Gherig’s Disease), and other neurological diseases.

Drs. Jeffrey Rothstein (Johns Hopkins ), B. T. Hyman (Mass General/Harvard Med), B. Eftekharzadeh (Biogen ), and J. G. Daigle (Abbvie) headed up a research group of some 20 other folks.  Their article, Tau Protein Disrupts Nuclecytoplasmic Transport in Alzheimer’s Disease, was just published in Neuron.

The data they present explains that the Tau tangles interfere with the action of the nuclear pore complex,  the gatekeeper that lets materials interact with the neuron.  In particular, they identified Nup98 as the nucleoporin most affected in the nuclear pore complex.  Nup98 is the building block for these nuclear pore complexes.  And, the Tau protein “sucks” Nup98 out of the nuclear pore complex.  It’s also possible that Nup98 may help the Tau protein aggregate and clump (which leads to cell death).

The problem is that we don’t know if the Nup98 interaction is the reason or the correlate of the situation.  A whole bunch of protein aggregates disrupt the transport between cytoplasm and the nucleus- and the actual mechanism by which that happens is unknown.

After all, we already saw that even when the Tau tangles disrupt nutrient transport, there is more to these Tau tangles than what first meets the eye.

That’s the next piece of research.  Because if it’s the reason, we have a clear method to control the Tau clumping (and, perhaps, Alzheimer’s).