Article
Neuroproteasomes regulate endogenous tau paired helical filament formation in an APOE genotype- and age-dependent manner.
Nature neuroscience - 1 Sept 2026
Paradise Victoria, Konrad-Vicario Kalin D, Nguyen Chi, Sharif Nyle A, Wang Xiao, Mukim Rijuta D, Sabu Malavika, Corjuc Bianca T, Bafia Joanna, Fu Jack, Maldonado Gabriella C, Strickland Michael, Grauman Sarah L, Figueroa Helen, Hyman Bradley T, Holtzman David M, Nuriel Tal, Ramachandran Kapil V
Abstract excerpt
In Alzheimer's disease (AD), endogenous tau undergoes a pathogenic transition to form paired helical filaments (PHFs), but the cellular mechanisms driving this process have been elusive. Here, we identify the neuron-specific plasma membrane proteasome ('neuroproteasome') as a critical determinant of tau proteostasis. Selective inhibition of neuroproteasome function rapidly triggers the de novo formation of...
Read the complete abstract on PubMedTopics
- Animals
- tau Proteins
- Humans
- Proteasome Endopeptidase Complex
- Neurons