Question about stopping Azilect, and apoptosis
 

I understand that Azilect (rasagiline) has been shown in some studies (but not all) to slow the progression of PD by interrupting the programmed cell death process (apoptosis). This allows diseased neurons to continue to live, and produce at least some level of dopamine, rather than "committing suicide" and producing none.

My question: If one has been taking Azilect for a few months or years, but then stops, how quickly does the cell death proceed? I could see two possibilities. Possibility 1: cell death occurs quickly after withdrawing Azilect, because many cells are in mid "cell death" process, held at the point of interruption. Without Azilect, those cells die rather quickly. Possibility 2: "cell death" resumes at the rate it would have done before, i.e. reasonably slowly.

Can anyone with a neurobiological background let me know which it is, or perhaps that it is a different possibility? This knowledge would be useful for anyone thinking of experimenting with a withdrawal of Azilect in order to assess medications, interactions, and so on.

Many Thanks

Dan Freedman (diagnosed 10 months ago, at age 50).

Dan, my reading of the evidence is that rasagiline blocks what is called the intrinsic pathway of apoptosis, mainly through preventing the release of cytochrome c from mitochondria.

This evidence, valuable as it is, has come mainly from cell culture and animal models.

I think that we will need to learn a lot more about this before we can extrapolate with any confidence about what might happen to a person who decides to discontinue rasagiline taken as treatment for PD.

Thanks for that info. If you happen to remember the names of any papers or researchers into rasagiline's effects on apoptosis, perhaps you could let me know.

Thanks

Dan

Most of the work has come from Naoi and colleagues in Japan.

Mitochondrial permeability transition mediates apoptosis induced by N-methyl(R)salsolinol, an endogenous neurotoxin, and is inhibited by Bcl-2 and ... - PubMed - NCBI
Functional mechanism of neuroprotection by inhibitors of type B monoamine oxidase in Parkinson's disease. - PubMed - NCBI
Revelation in the neuroprotective functions of rasagiline and selegiline: the induction of distinct genes by different mechanisms. - PubMed - NCBI
Rasagiline protects against alpha-synuclein induced sensitivity to oxidative stress in dopaminergic cells. - PubMed - NCBI
Rasagiline prevents cyclosporine A-sensitive superoxide flashes induced by PK11195, the initial signal of mitochondrial membrane permeabilization a... - PubMed - NCBI

Wonderful sources. Thanks.