Brain Glucose Hypometabolism and Brain Iron Accumulation as Therapeutic Targets for Alzheimer's Disease and Other CNS Disorders.

Two common mechanisms contributing to multiple neurological disorders, including Alzheimer's disease, are brain glucose hypometabolism (BGHM) and brain iron accumulation (BIA). Currently, BGHM and BIA are both widely acknowledged as biomarkers that aid in diagnosing CNS disorders, distinguishing between disorders with similar symptoms, and tracking disease progression. Therapeutics targeting BGHM and BIA in Alzheimer's disease can be beneficial in treating neurocognitive symptoms.

Intranasal Insulin Attenuates the Long-Term Adverse Effects of Neonatal Hyperglycemia on the Hippocampus in Rats.

Hyperglycemia due to relative hypoinsulinism is common in extremely preterm infants and is associated with hippocampus-mediated long-term cognitive impairment. In neonatal rats, hypoinsulinemic hyperglycemia leads to oxidative stress, altered neurochemistry, microgliosis, and abnormal synaptogenesis in the hippocampus. Intranasal insulin (INS) bypasses the blood-brain barrier, targets the brain, and improves synaptogenesis in rodent models, and memory in adult humans with Alzheimer's disease or type 2 diabetes, without altering the blood levels of insulin or glucose.

Losartan Improves Memory, Neurogenesis and Cell Motility in Transgenic Alzheimer's Mice.

Angiotensin receptor blockers (ARBs) have demonstrated multiple neuroprotective benefits in Alzheimer's disease (AD) models. However, their beneficial effects on memory deficits, cholinergic activity, neurogenesis and Amyloid beta (Aβ) clearance reveal significant interstudy variability. The delivery route can impact not only delivery but also targeting and therapeutic efficacy of ARBs.

Intranasal Insulin: a Treatment Strategy for Addiction.

Addiction to substances such as alcohol, cocaine, opioids, and methamphetamine poses a continuing clinical and public challenge globally. Despite progress in understanding substance use disorders, challenges remain in their treatment. Some of these challenges include limited ability of therapeutics to reach the brain (blood-brain barrier), adverse systemic side effects of current medications, and importantly key aspects of addiction not addressed by currently available treatments (such as cognitive impairment).

Pharmacokinetics in Rat of P8, a Peptide Drug Candidate for the Treatment of Alzheimer's Disease: Stability and Delivery to the Brain.

Strategies to achieve a therapy for Alzheimer's disease (AD) aimed at reducing the effects of amyloid-β (Aβ) have largely involved inhibiting or modifying the activities of the β- or -secretases or by the use of monoclonal antibodies (MAb). We previously offered the potential for a new, early and effective approach for the treatment of AD by a strategy that does not target the secretases. We showed that a family of peptides containing the DEEEDEEL sequence and another independent peptide, all derived from the amino terminus of PS-1, are each capable of markedly reducing the production of Aβ and in mThy1-hAPP transgenic mice.

Delivery of Nerve Growth Factor to the Brain via the Olfactory Pathway.

Purpose: To assess the potential of delivering nerve growth factor (NGF) to the brain along the olfactory neural pathway for the treatment of Alzheimer's disease. Methods: Recombinant human NGF (rhNGF) was given as nose drops to anesthetized rats. The rhNGF concentrations in the brain were determined by enzyme-linked immunosorbent assay (ELISA).