Nicotinamide, a Poly [ADP-Ribose] Polymerase 1 (PARP-1) Inhibitor, as an Adjunctive Therapy for the Treatment of Alzheimer’s Disease

Salech, Felipe; Ponce, Daniela P.; Paula-Lima, Andrea; SanMartín, Carol D.; Behrens, María I.

doi:10.3389/fnagi.2020.00255

Cited by 54 publications

(26 citation statements)

References 116 publications

(146 reference statements)

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“…Interestingly, FOXP3 also bound to TMPRSS2 which encoded another cell surface risk factor for SARS-CoV-2 infection [ 23 ]. Also, reduced APOE could reduce LRP1 inhibition of the TMPRSS2 activator PARP1, which in turn promotes the coronavirus infection as well (detailed pathway not shown) [ 34 , 35 ]. Therefore, APOE might regulate the infectivity of SARS-CoV-2 in multiple ways.…”

Section: Pathway Support For a Role Of Apoe4 In The Severity Of Covid-19mentioning

confidence: 99%

Severe COVID-19 in Alzheimer’s disease: APOE4’s fault again?

Xiong

Schiller

et al. 2021

Alz Res Therapy

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Challenges have been recognized in healthcare of patients with Alzheimer’s disease (AD) in the COVID-19 pandemic, given a high infection and mortality rate of COVID-19 in these patients. This situation urges the identification of underlying risks and preferably biomarkers for evidence-based, more effective healthcare. Towards this goal, current literature review and network analysis synthesize available information on the AD-related gene APOE into four lines of mechanistic evidence. At a cellular level, the risk isoform APOE4 confers high infectivity by the underlying coronavirus SARS-CoV-2; at a genetic level, APOE4 is associated with severe COVID-19; at a pathway level, networking connects APOE with COVID-19 risk factors such as ACE2, TMPRSS2, NRP1, and LZTFL1; at a behavioral level, APOE4-associated dementia may increase the exposure to coronavirus infection which causes COVID-19. Thus, APOE4 could exert multiple actions for high infection and mortality rates of the patients, or generally, with COVID-19.

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Section: Pathway Support For a Role Of Apoe4 In The Severity Of Covid-19mentioning

confidence: 99%

Severe COVID-19 in Alzheimer’s disease: APOE4’s fault again?

Xiong

Schiller

et al. 2021

Alz Res Therapy

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“…Inhibition of PARPs on the other hand, has been shown to increase NAD + levels and delay neuronal death associated with mitochondrial dysfunction in a PD fly model [74]. NAM is one such inhibitor of PARP-1 [120]. NAM supplementation has been shown to be protective against retinal ganglion cell neurodegeneration and prevented a number of early gene expression changes in D2 retinal ganglion cells [41].…”

Section: Parpmentioning

confidence: 99%

Neuroprotection in Glaucoma: NAD+/NADH Redox State as a Potential Biomarker and Therapeutic Target

Petriti

Williams

Lascaratos

et al. 2021

Cells

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Glaucoma is the leading cause of irreversible blindness worldwide. Its prevalence and incidence increase exponentially with age and the level of intraocular pressure (IOP). IOP reduction is currently the only therapeutic modality shown to slow glaucoma progression. However, patients still lose vision despite best treatment, suggesting that other factors confer susceptibility. Several studies indicate that mitochondrial function may underlie both susceptibility and resistance to developing glaucoma. Mitochondria meet high energy demand, in the form of ATP, that is required for the maintenance of optimum retinal ganglion cell (RGC) function. Reduced nicotinamide adenine dinucleotide (NAD+) levels have been closely correlated to mitochondrial dysfunction and have been implicated in several neurodegenerative diseases including glaucoma. NAD+ is at the centre of various metabolic reactions culminating in ATP production—essential for RGC function. In this review we present various pathways that influence the NAD+(H) redox state, affecting mitochondrial function and making RGCs susceptible to degeneration. Such disruptions of the NAD+(H) redox state are generalised and not solely induced in RGCs because of high IOP. This places the NAD+(H) redox state as a potential systemic biomarker for glaucoma susceptibility and progression; a hypothesis which may be tested in clinical trials and then translated to clinical practice.

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“…In addition, PARPs are enzymes that normally control DNA repair, whose overactivation under intense DNA oxidative damage may lead to cellular depletion of NAD+ and ATP. Both processes may promote cell death, potentially contributing to the pathogenesis of neurodegenerative disorders such as AD [103].…”

Section: The Role Of Nadh In Cell Metabolism and Antioxidant Defensementioning

confidence: 99%

“…Strikingly, this oxidative damage was reflected in lower resting levels of NAD(P)H/FAD fluorescence ratio and was fully reversible through treatment with NAM. Interestingly, it has been proposed that NAM, as well as other PARP-1 inhibitors, may be used as a treatment for AD at early stages [103]. In order to further test this therapeutic chance, it would be interesting to analyze the content of NADPH in AD patient-derived ONPs by FLIM during the treatment with PARP-1 inhibitors.…”

Section: Potential Monitoring Of Ad Progression Through Nadh Flimmentioning

confidence: 99%

Analyzing Olfactory Neuron Precursors Non-Invasively Isolated through NADH FLIM as a Potential Tool to Study Oxidative Stress in Alzheimer’s Disease

Gómez-Virgilio

Luarte

Ponce

et al. 2021

IJMS

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Among all the proposed pathogenic mechanisms to understand the etiology of Alzheimer’s disease (AD), increased oxidative stress seems to be a robust and early disease feature where many of those hypotheses converge. However, despite the significant lines of evidence accumulated, an effective diagnosis and treatment of AD are not yet available. This limitation might be partially explained by the use of cellular and animal models that recapitulate partial aspects of the disease and do not account for the particular biology of patients. As such, cultures of patient-derived cells of peripheral origin may provide a convenient solution for this problem. Peripheral cells of neuronal lineage such as olfactory neuronal precursors (ONPs) can be easily cultured through non-invasive isolation, reproducing AD-related oxidative stress. Interestingly, the autofluorescence of key metabolic cofactors such as reduced nicotinamide adenine dinucleotide (NADH) can be highly correlated with the oxidative state and antioxidant capacity of cells in a non-destructive and label-free manner. In particular, imaging NADH through fluorescence lifetime imaging microscopy (FLIM) has greatly improved the sensitivity in detecting oxidative shifts with minimal intervention to cell physiology. Here, we discuss the translational potential of analyzing patient-derived ONPs non-invasively isolated through NADH FLIM to reveal AD-related oxidative stress. We believe this approach may potentially accelerate the discovery of effective antioxidant therapies and contribute to early diagnosis and personalized monitoring of this devastating disease.

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Nicotinamide, a Poly [ADP-Ribose] Polymerase 1 (PARP-1) Inhibitor, as an Adjunctive Therapy for the Treatment of Alzheimer’s Disease

Cited by 54 publications

References 116 publications

Severe COVID-19 in Alzheimer’s disease: APOE4’s fault again?

Severe COVID-19 in Alzheimer’s disease: APOE4’s fault again?

Neuroprotection in Glaucoma: NAD+/NADH Redox State as a Potential Biomarker and Therapeutic Target

Analyzing Olfactory Neuron Precursors Non-Invasively Isolated through NADH FLIM as a Potential Tool to Study Oxidative Stress in Alzheimer’s Disease

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