I'm not sure if you've tried this yet:

https://clinicalproteomicsjournal.biomedcentral.com/articles/10.1186/1559-0275-11-4

They attempted to optimize the conditions for using tris(hydroxymethyl)aminomethane to extract protein from formalin-fixed, paraffin-embedded tissue. I would assume that if your samples are not embedded in paraffin, this should be even easier for you.

Hi Daniel,

Thanks for the reference.  Yes it was a very simple protocol and worked much better than other recipes I've tried.

Curious if you've had experience with it though, but I probably underestimated the amount of buffer to be used for my extraction in various tissue sections (ie: cortex, hippocampus), because I still notice some protein not migrating from the top of my gel (still cross linked), though there are bands down the lane where I expect.

I'll try re-incubating my samples in more buffer.  Although I hope these excessive heating steps don't denature and degrade my proteins.  These tissue lysates have actually gone through 2 cycles of heating already and I haven't noticed any small protein fragments on my blots.  So the proteins must be pretty hardy.