AMP‐activated protein kinase: a potential player in Alzheimer’s disease

• Published in: Journal of neurochemistry 2011-08, Vol.118 (4), p.460-474
• Main Authors: Salminen, Antero, Kaarniranta, Kai, Haapasalo, Annakaisa, Soininen, Hilkka, Hiltunen, Mikko
• Format: Article
• Language: English
• Subjects: Adult and adolescent clinical studies; aging; Alzheimer Disease - enzymology; Alzheimer Disease - genetics; Alzheimer's disease; AMP-Activated Protein Kinases - genetics; AMP-Activated Protein Kinases - metabolism; AMP-Activated Protein Kinases - physiology; AMPK; Amyloid - biosynthesis; Animals; autophagy; Autophagy - physiology; Biological and medical sciences; Calcium - metabolism; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Enzyme Activation - drug effects; Humans; inflammation; Inflammation - metabolism; Inflammation - pathology; Kinases; Leptin - physiology; Medical sciences; Metformin - pharmacology; Neurochemistry; Neurology; Neurons - physiology; Organic mental disorders. Neuropsychology; Phosphorylation; Protein synthesis; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Signal transduction; tau Proteins - metabolism; tauopathy
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2011.07331.x

J. Neurochem. (2011) 118, 460–474. AMP‐activated protein kinase (AMPK) stimulates energy production via glucose and lipid metabolism, whereas it inhibits energy consuming functions, such as protein and cholesterol synthesis. Increased cytoplasmic AMP and Ca2+ levels are the major activators of neuronal AMPK signaling. Interestingly, Alzheimer’s disease (AD) is associated with several abnormalities in neuronal energy metabolism, for example, decline in glucose uptake, mitochondrial dysfunctions and defects in cholesterol metabolism, and in addition, with problems in maintaining Ca2+ homeostasis. Epidemiological studies have also revealed that many metabolic and cardiovascular diseases are risk factors for cognitive impairment and sporadic AD. Emerging studies indicate that AMPK signaling can regulate tau protein phosphorylation and amyloidogenesis, the major hallmarks of AD. AMPK is also a potent activator of autophagic degradation which seems to be suppressed in AD. All these observations imply that AMPK is involved in the pathogenesis of AD. However, the responses of AMPK activation are dependent on stimulation and the extent of activating stress. Evidently, AMPK signaling can repress and delay the appearance of AD pathology but later on, with increasing neuronal stress, it can trigger detrimental effects that augment AD pathogenesis. We will outline the potential role of AMPK function in respect to various aspects affecting AD pathogenesis.