RABS

Rab associated diseases

Rab1

o Rab1A and Rab1B are found predominantly at the membrane of endoplasmic reticulum (ER) and Golgi. They have also been detected on lipid rafts and autophagasomes..

o Rab1 regulates ER to Golgi transport important for regulating growth migration and survival.

o Rab1 is found to upregulate growth in cancers such as colorectal cancer, hepatocellular carcinomas and breast cancer.

o Overexpression of rab1 can give a more potent cancer form than some oncogenes during testing in tumor formation by activating TORC1, inducing tumour growth invasion and progression. Overexpression can also lead to cardiomytrophy (thickening of heart muscle).

o Rab1 is also an important factor in Parkinson's disease, where overexpression protects golgi fragmentation by a protein formed in Parkinson's disease.

o Rab1 could be targeted to reduce its activity, reducing invasiveness of cancer or to enhance its activity to protect the golgi in Parkinson's disease 9

Rab6

o Rab6 is involved in retrograde ER / golgi trafficking, which is important in the unfolded protein response (UPR).

o Rab 6 is found to increase in expression with BiP, a chaperone protein found in the ER in UPR activation which has led to increasing evidence that Rab6 may help to modulate the UPR.

o In Alzheimer's disease, aggregates of misfolded proteins are accumulated in the ER, triggering the UPR which helps stop the accumulation of the misfolded proteins. BiP levels are elevated in the UPR along with Rab6 levels colocalised with BiP. This has given new possible therapeutic targets for Alzheimer's disease, whereby upregulating expression of rab6 may decrease the level of toxicity formed by the misfolded protein aggregates 10/11