Physical Exercise and Alzheimer’s Disease: Effects on Pathophysiological Molecular Pathways of the Disease

López-Ortiz, Susana; Pinto-Fraga, José; Martín-Hernández, Juan; Seisdedos, María M.; García-López, Óscar; Toschi, Nicola; Giuliano, Francesca Di; Garaci, Francesco; Mercuri, Nicola Biagio; Nisticò, Robert; Emanuele, Enzo; Lista, Simone; Lucía, Alejandro; Santos‐Lozano, Alejandro

doi:10.3390/ijms22062897

Cited by 46 publications

(39 citation statements)

References 201 publications

(338 reference statements)

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“…Overall, physical activity can not only improve redox status increasing neurotrophic factors and enzymes related to antioxidant, but also protect against cellular senescence through telomere-stabilizing proteins. With respect to its effects in AD, physical activity showed enhancement of Aβ degrading enzymes, thereby reducing Aβ plaques [ 394 , 395 ].…”

Section: Resultsmentioning

confidence: 99%

Recent Neurotherapeutic Strategies to Promote Healthy Brain Aging: Are we there yet?

Kim¹,

Sachdev²,

Braidy³

2022

Aging and disease

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Owing to the global exponential increase in population ageing, there is an urgent unmet need to develop reliable strategies to slow down and delay the ageing process. Age-related neurodegenerative diseases are among the main causes of morbidity and mortality in our contemporary society and represent a major socio-economic burden. There are several controversial factors that are thought to play a causal role in brain ageing which are continuously being examined in experimental models. Among them are oxidative stress and brain inflammation which are empirical to brain ageing. Although some candidate drugs have been developed which reduce the ageing phenotype, their clinical translation is limited. There are several strategies currently in development to improve brain ageing. These include strategies such as caloric restriction, ketogenic diet, promotion of cellular nicotinamide adenine dinucleotide (NAD + ) levels, removal of senescent cells, ‘young blood’ transfusions, enhancement of adult neurogenesis, stem cell therapy, vascular risk reduction, and non-pharmacological lifestyle strategies. Several studies have shown that these strategies can not only improve brain ageing by attenuating age-related neurodegenerative disease mechanisms, but also maintain cognitive function in a variety of pre-clinical experimental murine models. However, clinical evidence is limited and many of these strategies are awaiting findings from large-scale clinical trials which are nascent in the current literature. Further studies are needed to determine their long-term efficacy and lack of adverse effects in various tissues and organs to gain a greater understanding of their potential beneficial effects on brain ageing and health span in humans.

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Section: Resultsmentioning

confidence: 99%

Recent Neurotherapeutic Strategies to Promote Healthy Brain Aging: Are we there yet?

Kim¹,

Sachdev²,

Braidy³

2022

Aging and disease

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“…The major findings are as follows. Physical exercise can improve cognitive function and reduce the risk of AD [e.g., [44][45][46]. Patients with AD dementia have better outcomes including improved memory and cognitive behavior when they start exercising regularly [8,9,10,11,12,13,14,15,18,47].…”

Section: Discussionmentioning

confidence: 99%

The Effects of Physical Running on Dendritic Spines and Amyloid-Beta Pathology in 3xTg-AD Male Mice

et al. 2021

Preprint

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Background: Memory loss is the key symptom of Alzheimer's disease (AD). As successful drug treatments have not yet been identified, non-pharmaceutical intervention, such as physical exercise has been recognized as an effective strategy to improve memory function of people with dementia. Here we investigated the effect of prolonged physical running on hippocampal-dependent spatial memory and underlying mechanisms in 3xTg-AD mouse, a well-established rodent model of Alzheimer's disease (AD). Methods: 3xTg-AD transgenic mice with three AD mutations were used and compared with non-transgenic mice. Voluntary wheel running continued for 5 months (1 hour per day, 5 days per week) and was followed by spatial memory testing. At the end of behavior testing, dendritic spines, synapses, and synaptic proteins as well as amyloid-beta (Aβ) pathology were analyzed in the dorsal hippocampi. Results: Running improved hippocampal-dependent spatial memory in 3xTg-AD mice. This running strategy prevented both thin and mushroom-type spines on CA1 pyramidal cells in 3xTg-AD mice, whereas the effects of running in non-transgenic mice were limited to thin spines. The enormous effects of running on spines were accompanied by increased synapses and higher expressions of synaptic proteins. Notably, running downregulated the processing of amyloid precursor protein, resulting in reduced Aβ peptides, and spatial memory performance correlated with levels of Aβ peptides Aβ1-40 and Aβ1-42. Conclusion: These data suggest that prolonged running may improve memory in preclinical AD via slowing down amyloid pathology and preventing loss of synaptic contacts.

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“…A multimodal physical exercise program reduced fall risk and produced an improvement in gait, balance, and bone mineral density in the short and medium term in institutionalized patients with AD [ 283 ]. Regular physical exercise protects against AD by inhibiting different pathophysiological molecular pathways implicated in AD [ 284 ]. The beneficial effects of exercise in reducing the levels of Aβ were reviewed recently [ 285 ].…”

Section: Lifestyle Modificationsmentioning

confidence: 99%

Disentangling Mitochondria in Alzheimer’s Disease

Johri

2021

IJMS

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Alzheimer’s disease (AD) is a major cause of dementia in older adults and is fast becoming a major societal and economic burden due to an increase in life expectancy. Age seems to be the major factor driving AD, and currently, only symptomatic treatments are available. AD has a complex etiology, although mitochondrial dysfunction, oxidative stress, inflammation, and metabolic abnormalities have been widely and deeply investigated as plausible mechanisms for its neuropathology. Aβ plaques and hyperphosphorylated tau aggregates, along with cognitive deficits and behavioral problems, are the hallmarks of the disease. Restoration of mitochondrial bioenergetics, prevention of oxidative stress, and diet and exercise seem to be effective in reducing Aβ and in ameliorating learning and memory problems. Many mitochondria-targeted antioxidants have been tested in AD and are currently in development. However, larger streamlined clinical studies are needed to provide hard evidence of benefits in AD. This review discusses the causative factors, as well as potential therapeutics employed in the treatment of AD.

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Physical Exercise and Alzheimer’s Disease: Effects on Pathophysiological Molecular Pathways of the Disease

Cited by 46 publications

References 201 publications

Recent Neurotherapeutic Strategies to Promote Healthy Brain Aging: Are we there yet?

Recent Neurotherapeutic Strategies to Promote Healthy Brain Aging: Are we there yet?

The Effects of Physical Running on Dendritic Spines and Amyloid-Beta Pathology in 3xTg-AD Male Mice

Disentangling Mitochondria in Alzheimer’s Disease

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