Acetyl-L-Carnitine in Dementia and Other Cognitive Disorders: A Critical Update

Pennisi, Monica; Lanza, Giuseppe; Cantone, Mariagiovanna; D’Amico, Emanuele; Fisicaro, Francesco; Puglisi, Valentina; Vinciguerra, Luisa; Bella, Rita; Vicari, Enzo

doi:10.3390/nu12051389

Cited by 63 publications

(38 citation statements)

References 102 publications

(160 reference statements)

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“…Acylcarnitines are known to play a crucial role in stabilizing neuronal membranes and neurotransmission [ 51 ]. Supplementation of acylcarnitine has shown beneficial effects in treating chronic degenerative diseases [ 52 , 53 ]. However, there are still controversies regarding the dysregulation of production, synthesis, and carnitine/acylcarnitine extraction in SMA patients.…”

Section: Lipid Metabolic Abnormalities In Smamentioning

confidence: 99%

Metabolic and Nutritional Issues Associated with Spinal Muscular Atrophy

Chen

et al. 2020

Nutrients

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Spinal muscular atrophy (SMA), the main genetic cause of infant death, is a neurodegenerative disease characterized by the selective loss of motor neurons in the anterior horn of the spinal cord, accompanied by muscle wasting. Pathomechanically, SMA is caused by low levels of the survival motor neuron protein (SMN) resulting from the loss of the SMN1 gene. However, emerging research extends the pathogenic effect of SMN deficiency beyond motor neurons. A variety of metabolic abnormalities, especially altered fatty acid metabolism and impaired glucose tolerance, has been described in isolated cases of SMA; therefore, the impact of SMN deficiency in metabolic abnormalities has been speculated. Although the life expectancy of these patients has increased due to novel disease-modifying therapies and standardization of care, understanding of the involvement of metabolism and nutrition in SMA is still limited. Optimal nutrition support and metabolic monitoring are essential for patients with SMA, and a comprehensive nutritional assessment can guide personalized nutritional therapy for this vulnerable population. It has recently been suggested that metabolomics studies before and after the onset of SMA in patients can provide valuable information about the direct or indirect effects of SMN deficiency on metabolic abnormalities. Furthermore, identifying and quantifying the specific metabolites in SMA patients may serve as an authentic biomarker or therapeutic target for SMA. Here, we review the main epidemiological and mechanistic findings that link metabolic changes to SMA and further discuss the principles of metabolomics as a novel approach to seek biomarkers and therapeutic insights in SMA.

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Section: Lipid Metabolic Abnormalities In Smamentioning

confidence: 99%

Metabolic and Nutritional Issues Associated with Spinal Muscular Atrophy

Chen

et al. 2020

Nutrients

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“…Our findings suggest an important role for ROS in regulating BBB integrity during hypoxia as an upstream signaling pathway for FoxO3a-mediated degradation of claudin-5 and redistribution of ZO-1. Many natural compounds are known to be effective not only in neurodegenerative disorders, but also in VCI, through antioxidant mechanisms [ 51 , 52 , 53 ]. Consistent with our results, some of the natural flavonoids, such as epicatechin, cyanidin, and HSP, have been reported to have a neuroprotective effect through BBB protection, including permeability [ 53 ].…”

Section: Discussionmentioning

confidence: 99%

Yuzu and Hesperidin Ameliorate Blood-Brain Barrier Disruption during Hypoxia via Antioxidant Activity

Lee

Hyun

2020

Antioxidants

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Yuzu and its main component, hesperidin (HSP), have several health benefits owing to their anti-inflammatory and antioxidant properties. We examined the effects of yuzu and HSP on blood–brain barrier (BBB) dysfunction during ischemia/hypoxia in an in vivo animal model and an in vitro BBB endothelial cell model, and also investigated the underlying mechanisms. In an in vitro BBB endothelial cell model, BBB permeability was determined by measurement of Evans blue extravasation in vivo and in vitro. The expression of tight junction proteins, such as claudin-5 and zonula occludens-1 (ZO-1), was detected by immunochemistry and western blotting, and the reactive oxygen species (ROS) level was measured by 2′7′-dichlorofluorescein diacetate intensity. Yuzu and HSP significantly ameliorated the increase in BBB permeability and the disruption of claudin-5 and ZO-1 in both in vivo and in vitro models. In bEnd.3 cells, yuzu and HSP were shown to inhibit the disruption of claudin-5 and ZO-1 during hypoxia, and the protective effects of yuzu and HSP on claudin-5 degradation seemed to be mediated by Forkhead box O 3a (FoxO3a) and matrix metalloproteinase (MMP)-3/9. In addition, well-known antioxidants, trolox and N-acetyl cysteine, significantly attenuated the BBB permeability increase, disruption of claudin-5 and ZO-1, and FoxO3a activation during hypoxia, suggesting that ROS are important mediators of BBB dysfunction during hypoxia. Collectively, these results indicate that yuzu and HSP protect the BBB against dysfunction via maintaining integrity of claudin-5 and ZO-1, and these effects of yuzu and HSP appear to be a facet of their antioxidant properties. Our findings may contribute to therapeutic strategies for BBB-associated neurodegenerative diseases.

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“…To date, an early identification and prompt management of cardio- and cerebrovascular risk factors are the only effective measures to prevent dementia and other types of cognitive disorders, such as Mild Cognitive Impairment (MCI) and VCI [ 21 , 22 ]. Therefore, a comprehensive description and quantification of these factors is the preliminary step towards the elucidation of the causes and mechanisms underlying the onset and progression of dementia, as well as the design of new disease-modifying strategies [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ].…”

Section: Introductionmentioning

confidence: 99%

Moderate Mocha Coffee Consumption Is Associated with Higher Cognitive and Mood Status in a Non-Demented Elderly Population with Subcortical Ischemic Vascular Disease

et al. 2021

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To date, interest in the role of coffee intake in the occurrence and course of age-related neurological and neuropsychiatric disorders has provided an inconclusive effect. Moreover, no study has evaluated mocha coffee consumption in subjects with mild vascular cognitive impairment and late-onset depression. We assessed the association between different quantities of mocha coffee intake over the last year and cognitive and mood performance in a homogeneous sample of 300 non-demented elderly Italian subjects with subcortical ischemic vascular disease. Mini Mental State Examination (MMSE), Stroop Colour-Word Interference Test (Stroop T), 17-items Hamilton Depression Rating Scalfe (HDRS), Activities of Daily Living (ADL), and Instrumental ADL were the outcome measures. MMSE, HDRS, and Stroop T were independently and significantly associated with coffee consumption, i.e., better scores with increasing intake. At the post-hoc analyses, it was found that the group with a moderate intake (two cups/day) had similar values compared to the heavy drinkers (≥three cups/day), with the exception of MMSE. Daily mocha coffee intake was associated with higher cognitive and mood status, with a significant dose-response association even with moderate consumption. This might have translational implications for the identification of modifiable factors for vascular dementia and geriatric depression.

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Acetyl-L-Carnitine in Dementia and Other Cognitive Disorders: A Critical Update

Cited by 63 publications

References 102 publications

Metabolic and Nutritional Issues Associated with Spinal Muscular Atrophy

Metabolic and Nutritional Issues Associated with Spinal Muscular Atrophy

Yuzu and Hesperidin Ameliorate Blood-Brain Barrier Disruption during Hypoxia via Antioxidant Activity

Moderate Mocha Coffee Consumption Is Associated with Higher Cognitive and Mood Status in a Non-Demented Elderly Population with Subcortical Ischemic Vascular Disease

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