Autophagy in Alzheimer’s disease pathogenesis: Therapeutic potential and future perspectives

Ageing Research Reviews, Journal Year: 2021, Volume and Issue: 72, P. 101464 - 101464

Published: Sept. 20, 2021

Alzheimer's disease (AD) is a complex neurodegenerative in the elderly and most common cause of human dementia. AD characterized by accumulation abnormal protein aggregates including amyloid plaques (composed beta-amyloid (Aβ) peptides) neurofibrillary tangles (formed hyper-phosphorylated tau protein). Synaptic plasticity, neuroinflammation, calcium signaling etc. also show dysfunction patients. Autophagy an evolutionarily conserved lysosome-dependent cellular event eukaryotes. It closely linked to modulation metabolism, through which damaged organelles mis-folded proteins are degraded then recycled maintain homeostasis. Accumulating evidence has shown that impaired autophagy contributes pathogenesis. In present review, we highlight role autophagy, bulk selective regulating metabolic circuits We discuss potential future perspectives autophagy-inducing strategies therapeutics.

Language: Английский

---

Metformin in aging and aging-related diseases: clinical applications and relevant mechanisms

Theranostics, Journal Year: 2022, Volume and Issue: 12(6), P. 2722 - 2740

Published: Jan. 1, 2022

Aging is a natural process, which plays critical role in the pathogenesis of variety diseases, i.e., aging-related such as diabetes, osteoarthritis, Alzheimer disease, cardiovascular cancers, obesity and other metabolic abnormalities.Metformin, most widely used antidiabetic drug, has been reported to delay aging display protective effect on attenuating progression various diseases by impacting key hallmark events aging, including dysregulated nutrient sensing, loss proteostasis, mitochondrial dysfunction, altered intercellular communication, telomere attrition, genomic instability, epigenetic alterations, stem cell exhaustion cellular senescence.In this review, we provide updated information knowledge applications metformin prevention treatment diseases.We focus our discussions roles underlying mechanisms modulating treating diseases.

Language: Английский

---

LAMP2A, LAMP2B and LAMP2C: similar structures, divergent roles

Autophagy, Journal Year: 2023, Volume and Issue: 19(11), P. 2837 - 2852

Published: July 20, 2023

LAMP2 (lysosomal associated membrane protein 2) is one of the major components lysosomal membrane. There currently exist three isoforms, LAMP2A, LAMP2B and LAMP2C, they vary in distribution function. LAMP2A serves as a receptor channel for transporting cytosolic proteins process called chaperone-mediated autophagy (CMA). required autophagosome-lysosome fusion cardiomyocytes exosome membranes. LAMP2C primarily implicated novel type which nucleic acids are taken up into lysosomes degradation. In this review, current evidence function each isoform various pathophysiological processes human diseases, well their possible mechanisms, comprehensively summarized. We discuss evolutionary patterns isoforms vertebrates provide technical guidance on investigating these isoforms. also concerned with newly arising questions particular research area that remain unanswered. Advances functions will uncover new links between dysfunction, diseases.Abbreviation: ACSL4: acyl-CoA synthetase long-chain family member 4; AD: Alzheimer disease; Ag: antigens; APP: amyloid beta precursor protein; ATG14: related 14; AVSF: autophagic vacuoles unique sarcolemmal features; BBC3/PUMA: BCL2 binding component 3; CCD: C-terminal coiled coil domain; CMA: autophagy; CVDs: cardiovascular diseases; DDIT4/REDD1: DNA damage inducible transcript ECs: endothelial cells; ER: endoplasmic reticulum; ESCs: embryonic stem GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GBA/β-glucocerebrosidase: glucosylceramidase beta; GSCs: glioblastoma HCC: hepatocellular carcinoma; HD: Huntington HSCs: hematopoietic HSPA8/HSC70: heat shock A (Hsp70) 8; IL3: interleukin IR: ischemia-reperfusion; LAMP2: 2; LDs: lipid droplets; LRRK2: leucine rich repeat kinase MA: macroautophagy; MHC: histocompatibility complex; MST1: macrophage stimulating 1; NAFLD: nonalcoholic fatty liver NFE2L2/NRF2: NFE2 like bZIP transcription factor NLRP3: NLR pyrin domain containing PARK7: Parkinsonism deglycase; PD: Parkinson PEA15/PED: proliferation apoptosis adaptor 15; PKM/PKM2: pyruvate M1/2; RA: rheumatoid arthritis; RARA: retinoic acid alpha; RCAN1: regulator calcineurin RCC: renal cell RDA: RNautophagy DNautophagy; RNAi: RNA interference; RND3: Rho Family GTPase SG-NOS3/eNOS: deleterious glutathionylated NOS3; SLE: systemic lupus erythematosus; TAMs: tumor-associated macrophages; TME: tumor microenvironment; UCHL1: ubiquitin hydrolase L1; VAMP8: vesicle 8.

Language: Английский

---

Long-term use of metformin and Alzheimer’s disease: beneficial or detrimental effects

Inflammopharmacology, Journal Year: 2023, Volume and Issue: 31(3), P. 1107 - 1115

Published: Feb. 28, 2023

Language: Английский

---

The interaction between ageing and Alzheimer's disease: insights from the hallmarks of ageing

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Jan. 23, 2024

Abstract Ageing is a crucial risk factor for Alzheimer’s disease (AD) and characterised by systemic changes in both intracellular extracellular microenvironments that affect the entire body instead of single organ. Understanding specific mechanisms underlying role ageing development can facilitate treatment ageing-related diseases, such as AD. Signs brain have been observed AD patients animal models. Alleviating pathological caused dramatically ameliorate amyloid beta- tau-induced neuropathological memory impairments, indicating plays pathophysiological process In this review, we summarize impact several age-related factors on propose preventing promising strategy improving cognitive health.

Language: Английский

---

Role of ketogenic diet in neurodegenerative diseases focusing on Alzheimer diseases: The guardian angle

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 95, P. 102233 - 102233

Published: Feb. 14, 2024

Language: Английский

---

Targeting the Interplay Between Autophagy and the Nrf2 Pathway in Parkinson’s Disease with Potential Therapeutic Implications

Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 149 - 149

Published: Jan. 19, 2025

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder marked by the progressive degeneration of midbrain dopaminergic neurons and resultant locomotor dysfunction. Despite over two centuries recognition as chronic disease, exact pathogenesis PD remains elusive. The onset progression involve multiple complex pathological processes, with dysfunctional autophagy elevated oxidative stress serving critical contributors. Notably, emerging research has underscored interplay between in pathogenesis. Given limited efficacy therapies targeting either dysfunction or stress, it crucial to elucidate intricate mechanisms governing their develop more effective therapeutics. This review overviews role nuclear factor erythroid 2-related 2 (Nrf2), pivotal transcriptional regulator orchestrating cellular defense against these processes. By elucidating key processes PD, this will deepen our comprehensive understanding multifaceted underlying may uncover potential strategies for its prevention treatment.

Language: Английский

---

Advancements in autophagy perturbations in Alzheimer’s disease: Molecular aspects and therapeutics

Brain Research, Journal Year: 2025, Volume and Issue: 1851, P. 149494 - 149494

Published: Feb. 6, 2025

Language: Английский

---

Glucose metabolism and AD: evidence for a potential diabetes type 3

Alzheimer s Research & Therapy, Journal Year: 2022, Volume and Issue: 14(1)

Published: April 20, 2022

Alzheimer's disease is the most prevalent cause of dementia in elderly. Neuronal death and synaptic dysfunctions are considered main hallmarks this disease. The latter could be directly associated to an impaired metabolism. In particular, glucose metabolism impairment has demonstrated a key regulatory element onset progression AD, which why nowadays AD type 3 diabetes.

Language: Английский

---

Mechanism of metformin regulation in central nervous system: Progression and future perspectives

Biomedicine & Pharmacotherapy, Journal Year: 2022, Volume and Issue: 156, P. 113686 - 113686

Published: Oct. 13, 2022

Metformin as a first-line drug for type 2 diabetes mellitus(T2DM) treatment is widely studied. can reduce liver glucose output and improve insulin resistance. Recent evidence from in vivo vitro has confirmed that metformin transport across the blood-brain barrier(BBB) activate specific neurons neuroglia to exert neurological actions, however, effect of regulation on CNS still obscure. In this review, we summarized current preclinical focusing regulatory role found potential neuroprotective, neurotrophic, neurogenesis-stimulated actions; besides, also exerts antiinflammatory by inhibiting microglial activates regulating polarization. These findings indicate there might be extensive pharmacological efficacy therapeutic insights diseases' clinical application.

Language: Английский

---