Lactate links exercise to synaptic protection and cognitive enhancement in Alzheimer’s disease models DOI Creative Commons
Hao Han, Yi Wu,

Rivkin Mi

и другие.

BMC Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Июнь 3, 2025

Physical exercise is known to promote cognitive resilience in aging and Alzheimer's disease (AD), but the underlying mechanisms remain incompletely understood. Lactate, a metabolic byproduct elevated during exercise, has recently emerged as potential neuromodulator of brain function. Three AD-like mouse models (SAMP8, Aβ1-42 injection, 5xFAD) were used evaluate effects treadmill on function synaptic plasticity. Serum lactate levels assessed, sodium L-lactate (NaLA) was administered determine its neuroprotective effects. Transcriptomic analysis performed hippocampal tissue explore lactate-regulated pathways. Lactate transport pharmacologically inhibited using 4-CIN for mechanistic validation. Treadmill significantly improved performance increased synapse-associated protein expression AD models. Exercise serum levels, exogenous NaLA administration recapitulated benefits exercise. profiling revealed enrichment genes involved axon guidance organization, including upregulation multiple Eph receptor family genes. α-cyano-4-hydroxycinnamic acid (4-CIN) abolished exercise-induced effects, confirming essential role mediating these benefits. This study identifies critical mediator linking enhanced improvement models, providing insights highlighting metabolism therapeutic target AD.

Язык: Английский

Exercise training exerts beneficial effects on Alzheimer’s disease through multiple signaling pathways DOI Creative Commons
Jihe Kang,

Mei Liu,

Qiang Yang

и другие.

Frontiers in Aging Neuroscience, Год журнала: 2025, Номер 17

Опубликована: Май 21, 2025

Alzheimer’s disease (AD) is a neurodegenerative characterized by progressive memory loss and cognitive dysfunction that affects millions of people worldwide, placing massive burden on families economies. Exercise training can effectively reduce the prevalence AD alleviate its symptoms through modulation multiple signaling pathways involved in pathophysiological process AD, including PI3K/Akt, Wnt/β-catenin, AMPK-related, MAPK, NF-κB, PINK1-PARKIN, JAK/STAT, TREM2 pathways. Different also crosstalk with each other different targets to inhibit formation Amyloid β (Aβ) plaques, level hyperphosphorylated tau protein, apoptosis, relieve neuroinflammation, autophagy dysfunction, ultimately improve impairment patients. This review summarizes processes affected exercise We further provide reference for future development new effective prevention treatment develop promising personalized, combined intervention strategies.

Язык: Английский

Процитировано

0
Lactate links exercise to synaptic protection and cognitive enhancement in Alzheimer’s disease models DOI Creative Commons
Hao Han, Yi Wu,

Rivkin Mi

и другие.

BMC Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Июнь 3, 2025

Physical exercise is known to promote cognitive resilience in aging and Alzheimer's disease (AD), but the underlying mechanisms remain incompletely understood. Lactate, a metabolic byproduct elevated during exercise, has recently emerged as potential neuromodulator of brain function. Three AD-like mouse models (SAMP8, Aβ1-42 injection, 5xFAD) were used evaluate effects treadmill on function synaptic plasticity. Serum lactate levels assessed, sodium L-lactate (NaLA) was administered determine its neuroprotective effects. Transcriptomic analysis performed hippocampal tissue explore lactate-regulated pathways. Lactate transport pharmacologically inhibited using 4-CIN for mechanistic validation. Treadmill significantly improved performance increased synapse-associated protein expression AD models. Exercise serum levels, exogenous NaLA administration recapitulated benefits exercise. profiling revealed enrichment genes involved axon guidance organization, including upregulation multiple Eph receptor family genes. α-cyano-4-hydroxycinnamic acid (4-CIN) abolished exercise-induced effects, confirming essential role mediating these benefits. This study identifies critical mediator linking enhanced improvement models, providing insights highlighting metabolism therapeutic target AD.

Язык: Английский

Процитировано

0