NMN supplementation rescues aging-induced blood-brain barrier damage

The blood-brain barrier (BBB) is a critical component of the central nervous system that regulates the exchange of molecules between the brain and the bloodstream. Age-related changes in the BBB can lead to increased permeability and neuroinflammation, which are associated with cognitive decline and neurodegenerative diseases.
The authors discuss the role of nicotinamide mononucleotide (NMN), a precursor of NAD+, in maintaining BBB integrity. Researchers demonstrated that NMN supplementation can activate the CX43-PARP1 pathway, which promotes DNA repair and reduces oxidative stress, thereby improving BBB function and reducing neuroinflammation in aging mice. And NMN supplementation improved cognitive function in aged mice, suggesting that NAD+ may have neuroprotective effects in addition to its role in maintaining BBB function. (as shown in Figure 1)NMN supplementation may be a promising therapeutic strategy for treating age-related neurological disorders by targeting the CX43-PARP1 pathway and maintaining BBB integrity.

Figure 1

1. The CX43-PARP1-NAD+ pathway and its role in BBB function

The authors discuss the CX43-PARP1-NAD+ pathway, which plays a crucial role in maintaining BBB integrity. They demonstrate that NAD+ supplementation can rescue aging-induced BBB damage by activating the CX43-PARP1 pathway, which promotes DNA repair and reduces oxidative stress. The authors also show that NMN supplementation can upregulate NAD+ levels and activate the CX43-PARP1 pathway, thereby improving BBB function and reducing neuroinflammation in aging mice.(as shown in Figure 2)

  
Figure 2
 

These findings suggest that the CX43-PARP1-NAD+ pathway is a promising target for developing therapeutic interventions to maintain BBB integrity and prevent age-related neurological disorders.

2. NMN supplementation effects of long-term dietary interventions on BBB permeability in aging mice

To investigate the potential therapeutic benefits of NAD+ supplementation, the authors conducted a series of experiments using aging mice. They tested the effects of long-term dietary interventions with NMN or olaparib, a PARP1 inhibitor, on BBB permeability and cognitive function. They found that both interventions improved BBB integrity and reduced neuroinflammation in aging mice. (as shown in Figure 3)Furthermore, NMN supplementation improved cognitive function in aged mice, suggesting that NAD+ may have neuroprotective effects in addition to its role in maintaining BBB function. Researchers also observed that NMN supplementation increased the expression of tight junction proteins, which are critical for maintaining BBB integrity. These findings suggest that NMN supplementation may be a promising therapeutic strategy for preventing age-related BBB dysfunction and cognitive decline.(as shown in Figure 4)

Figure 3

Figure 4

3. Implications for treating age-related neurological disorders

NMN supplementation may be a promising therapeutic strategy for treating age-related neurological disorders finally. By targeting the CX43-PARP1 pathway and maintaining BBB integrity, NMN supplementation may prevent or delay the onset of neurodegenerative diseases such as Alzheimer's and Parkinson's. 
It also suggested that NMN supplementation may have broader implications for aging research, as NAD+ plays a critical role in cellular metabolism and DNA repair. What's more, studies should investigate the long-term effects of NMN supplementation on BBB function and cognitive decline in humans, as well as the potential side effects and optimal dosages of NMN supplementation.(as shown in Figure 5)

Figure 5

Overall,findings highlight the potential of NMN supplementation as a safe and effective therapeutic strategy for maintaining BBB function and preventing age-related neurological disorders.
 

Reference: Zhan et al., NAD + rescues aging-induced blood-brain barrier damage via the CX43-PARP1 axis, Neuron (2023),
//doi.org/10.1016/j.
 

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