Does vesicle fusion within the process of intraneuron recycling deserve more attention when it comes to researching dementia? Could TRPML1-3 be involved?

Last night I was reading this article--"Pathogenic cascades in lysosomal disease-Why so complex?" (J Inherit Metab Dis. 2009 Apr; 32(2): 181–189; full text online at http://europepmc.org/article/MED/19130290), and it occurred to me that some health problems that we associate with reduced autophagy (i.e., impaired autophagic function), ones such as Alzheimer's, Parkinson's, and Huntington's, are more likely to be caused by impaired reforming of intra-cell functions than by reduced autophagy per se. I think the reduced autophagy is the body's feedback mechanisms trying to slow down the recycling of cellular parts because something is not working correctly in the recycling process. 

Here's an excerpt from the article that caught my eye:

Lysosomal diseases are also caused by defects in soluble and membrane-associated non-enzyme proteins of late endosomes and lysosomes believed essential for the processes of substrate degradation and egress, as well as vesicle fusion....

Like NPC1 and NPC2 described above, defects in other enigmatic proteins have similarly been linked to lysosomal disease. For example, mutations in the MCOLN1 gene which codes mucolipin-1, a lysosomal membrane TRP (Transient Receptor Potential) family of ion channel, causes mucolipidosis type IV (MLIV) disease (Zeevi, et al., 2007). In spite of its name MLIV has little connection other than historic with MLII/III diseases which are caused by defects in the phosphotransferase enzyme responsible for adding the mannose-6 phosphate moiety to lysosomal enzymes as required for normal targeting to lysosomes. Like NPC1, mucolipin-1 resides in the membrane of late endosomes/lysosomes and while implicated in lysosomal pH control and in membrane fusion/fission events, its function remains essentially unknown. A similar situation exists for many of the proteins implicated in the ten (CLN1-CLN10) so-called neuronal ceroid lipofuscinoses, or Batten diseases (Kyttälä, et al., 2006). The CLN3 protein, for example, defects in which cause juvenile Batten disease, may be associated with autophagolysosomes fusion/maturation (Cao, et al., 2006), in lysosomal pH control (Pearce, et al., 1999), or a host of other functions (Rakheja, et al., 2008). Similarly, the CLN6 and CLN8 proteins are believed localized to membranes of the ER and while their absence leads to lysosomal storage, their functional link to lysosomes is unknown (Kyttälä, et al., 2006).

I'm most intrigued by the mucolipin mentioned above. There are now three mucolipins identified, TRPML1, TRPML 2, and TRPML3, as well as promoters and inhibitors of them. It would be interesting to see how they affect intraneuron recycling processes and whether they are involved in the development of dementia.