J-147 Powder - 2g,

J-147 is a potent neuroprotective and neurotrophic compound that protects against neurotoxicity in cortical neurons in vitro (EC₅₀ = 25 - 200 nM). Reduces soluble Aβ40 and Aβ42 levels and increases BDNF levels in the hippocampus in vivo. J 147 has been shown to enhance memory in normal animals and to prevent memory deficits in an Alzheimer’s disease mouse model. These effects are associated with an increase in brain derived neurotrophic factor levels, enhanced long-term potentiation, preservation of synaptic proteins, a reduction of markers for oxidative stress and inflammation, a reduction of amyloid plaques, and lower levels of soluble amyloid β.

"J147 is an exciting new compound because it really has strong potential to be an Alzheimer's disease therapeutic by slowing disease progression and reversing memory deficits following short-term treatment," says lead study author Marguerite Prior, a research associate in Salk's Cellular Neurobiology Laboratory.

J147 was developed at Salk in the laboratory of David Schubert, a professor in the Cellular Neurobiology Laboratory. He and his colleagues bucked the trend within the pharmaceutical industry, which has focused on the biological pathways involved in the formation of amyloid plaques, the dense deposits of protein that characterize the disease. Instead, the Salk team used living neurons grown in laboratory dishes to test whether their new synthetic compounds, which are based upon natural products derived from plants, were effective at protecting brain cells against several pathologies associated with brain aging. From the test results of each chemical iteration of the lead compound, they were able to alter their chemical structures to make them much more potent. Although J147 appears to be safe in mice, the next step will require clinical trials to determine whether the compound will prove safe and effective in humans.

To test the efficacy of J147 in a much more rigorous preclinical Alzheimer's model, the Salk team treated mice using a therapeutic strategy that they say more accurately reflects the human symptomatic stage of Alzheimer's. Administered in the food of 20-month-old genetically engineered mice, at a stage when Alzheimer's pathology is advanced, J147 rescued severe memory loss, reduced soluble levels of amyloid, and increased neurotrophic factors essential for memory, after only three months of treatment.

Prior and her colleagues say that several cellular processes known to be associated with Alzheimer's pathology are affected by J147, including an increase in a protein called brain-derived neurotrophic factor (BDNF), which protects neurons from toxic insults, helps new neurons grow and connect with other brain cells, and is involved in memory formation. Postmortem studies show lower than normal levels of BDNF in the brains of people with Alzheimer's.

Because of its broad ability to protect nerve cells, the researchers believe that J147 may also be effective for treating other neurological disorders, such as Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis (ALS), as well as stroke, although their study did not directly explore the drug's efficacy as a therapy for those diseases.