Deoxynucleoside triphosphate triphosphohydrolase SAMHD1

SAMHD1 (deoxynucleoside triphosphate triphosphohydrolase) is a 626-amino-acid protein with dual roles as a host restriction factor against viral infection and a regulator of DNA replication fork dynamics (UniProt: Q9Y3Z3). Its dNTPase activity depletes cellular dNTP pools to suppress HIV-1 and LINE-1 retrotransposon replication, while its dNTPase-independent function promotes DNA end resection at stalled replication forks, preventing chronic interferon-mediated inflammation.

SAMHD1 is implicated in Aicardi-Goutieres syndrome 5 and chilblain lupus 2, both associated with innate immune dysregulation and neuroinflammation (UniProt: Q9Y3Z3). The protein's role in suppressing interferon responses and managing DNA damage stress places it within pathways relevant to neurological homeostasis.

SAMHD1 is upregulated in Alzheimer's disease brain tissue, with a mean log2 fold-change of 0.36 in post-mortem AD versus age-matched controls (Chaparral AD proteomics). This elevation may reflect increased DNA damage stress or altered innate immune signaling in the AD brain environment, though the functional consequences remain to be established.