Sig-1R knockout or Sig-1R blockade treatment worsened neurotoxicity and behavioral deficits [49], while several agonists, including PRE-084, exhibited neuroprotection in animal models of Parkinson’s [50] and Alzheimer’s diseases [41,51,52,53,54]. The gene discussed is SIGMAR1; the disease is early-onset autosomal dominant Alzheimer disease.