Beneficial effects of lysosome-modulating and other pharmacological and nanocarrier agents on amyloid-beta-treated cells.
The progression of Alzheimer's disease (AD) is accompanied by disturbances of the endosome/lysosome (EL) system and there is accumulation of peptides of the AD-associated amyloid beta (Abeta) type in EL vesicles of affected neurons. EL modulating agents partially ameliorate the Abeta-mediated cell abnormalities. However, no extensive studies on the potential pharmaceutical applications of combinations of such agents and their synergistic effects have been performed. This study shows the beneficial anti-amyloid effects of several combinations of lysosomal modulators and other pharmacological and new nanobiotechnological agents. Some agents potentiated each other's action and some of them facilitated the anti-amyloid actions of memantine, a modifier of Ca2+-permeable channels involved in AD and one of the few drugs used for treatment of AD. Another compound used in nanobiotechnology ameliorated as a nanocarrier the beneficial effects of some of these potential pharmaceutical agents. They may be considered as additional drugs to improve the efficacy of the therapeutic approaches for AD and related neurodegenerative disorders.
Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, Brigham & Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Marie V
MV
Kanazirska
Philipp M
PM
Fuchs
Liping
L
Chen
Sumit
S
Lal
Jyoti
J
Verma
Peter M
PM
Vassilev
D000108:Acetylcarnitine / Q000494:pharmacology; D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D011992:Endosomes / Q000187:drug effects; D006801:Humans; D044949:Kaempferols / Q000494:pharmacology; D019344:Lactic Acid / Q000737:chemistry; D008247:Lysosomes / Q000187:drug effects*; D008559:Memantine / Q000494:pharmacology; D015735:Mifepristone / Q000737:chemistry; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D004337:Drug Carriers; D044949:Kaempferols; D018696:Neuroprotective Agents; D013267:Stilbenes; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D015735:Mifepristone; D019344:Lactic Acid; D000108:Acetylcarnitine; C006552:kaempferol; D000077185:Resveratrol; D008559:Memantine