If Murgab(TJ) to Sary Tash (KG) is closed, then there's only Samarkand (UZ) to Dushanbe (TJ).
There are 2 main routes Dushanbe to Khorog, so you don't have to ride the same road twice.
In addition to the M41 "Pamir Highway", there's also the Wakhan valley (along the Afghan border) and the Bartang valley, so you can choose 2 from 3 in order not to retrace your tyre tracks.
One of my all time favourite rides was the Bartang valley, particularly because it was a bit tricky and remote in places.
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