BACKGROUND: The pathomechanism of Alzheimer's disease (AD) is multifactorial although the most popular hypotheses are centered on the effects of the misfolded, aggregated protein, amyloid beta (Abeta) and on Tau hyperphosphorylation. OBJECTIVES: Double blinded clinical trials were planned to demonstrate the effect of Colostrinin (CLN) on instrumental daily activities of AD patients. The potential molecular mechanisms by which CLN mediates its effects were investigated by gene expression profiling. METHODS: RNAs isolated from CLN-treated cells were analyzed by high-density oligonucleotide arrays. Network and pathway analyses were performed using the Ingenuity Pathway Analysis software. RESULTS: The Full Sample Analysis at week 15 showed a stabilizing effect of CLN on cognitive function in ADAS-cog (p = 0.02) and on daily function in IADL (p = 0.02). The overall patient response was also in favor of CLN (p = 0.03). Patients graded as mild on entry also showed a superior response of ADAS-cog compared to more advanced cases (p = 0.01). Data derived from microarray network analysis show that CLN elicits highly complex and multiphasic changes in the cells' transcriptome. Importantly, transcriptomal analysis showed that CLN alters gene expression of molecular networks implicated in Abeta precursor protein synthesis, Tau phosphorylation and increased levels of enzymes that proteolitically eliminate Abeta. In addition, CLN enhanced the defense against oxidative stress and decreased expression of inflammatory chemokines and cytokines, thereby attenuating inflammatory processes that precede Alzheimer's and other neurological diseases. CONCLUSION: Together these data suggest that CLN has promising potential for clinical use in prevention and therapy of Alzheimer's and other age-associated central nervous system diseases.
BACKGROUND: The pathomechanism of Alzheimer's disease (AD) is multifactorial although the most popular hypotheses are centered on the effects of the misfolded, aggregated protein, amyloid beta (Abeta) and on Tau hyperphosphorylation. OBJECTIVES: Double blinded clinical trials were planned to demonstrate the effect of Colostrinin (CLN) on instrumental daily activities of ADpatients. The potential molecular mechanisms by which CLN mediates its effects were investigated by gene expression profiling. METHODS: RNAs isolated from CLN-treated cells were analyzed by high-density oligonucleotide arrays. Network and pathway analyses were performed using the Ingenuity Pathway Analysis software. RESULTS: The Full Sample Analysis at week 15 showed a stabilizing effect of CLN on cognitive function in ADAS-cog (p = 0.02) and on daily function in IADL (p = 0.02). The overall patient response was also in favor of CLN (p = 0.03). Patients graded as mild on entry also showed a superior response of ADAS-cog compared to more advanced cases (p = 0.01). Data derived from microarray network analysis show that CLN elicits highly complex and multiphasic changes in the cells' transcriptome. Importantly, transcriptomal analysis showed that CLN alters gene expression of molecular networks implicated in Abeta precursor protein synthesis, Tau phosphorylation and increased levels of enzymes that proteolitically eliminate Abeta. In addition, CLN enhanced the defense against oxidative stress and decreased expression of inflammatory chemokines and cytokines, thereby attenuating inflammatory processes that precede Alzheimer's and other neurological diseases. CONCLUSION: Together these data suggest that CLN has promising potential for clinical use in prevention and therapy of Alzheimer's and other age-associated central nervous system diseases.
Authors: Jerzy Leszek; Anna D Inglot; Maria Janusz; Franciszek Byczkiewicz; Andrzej Kiejna; Jerzy Georgiades; Józef Lisowski Journal: Med Sci Monit Date: 2002-10
Authors: D E Kang; C U Pietrzik; L Baum; N Chevallier; D E Merriam; M Z Kounnas; S L Wagner; J C Troncoso; C H Kawas; R Katzman; E H Koo Journal: J Clin Invest Date: 2000-11 Impact factor: 14.808
Authors: Luis Daniel Goyzueta-Mamani; Haruna Luz Barazorda-Ccahuana; Miguel Angel Chávez-Fumagalli; Karla Lucia F Alvarez; Jorge Alberto Aguilar-Pineda; Karin Jannet Vera-Lopez; Christian Lacks Lino Cardenas Journal: Molecules Date: 2022-01-28 Impact factor: 4.411