Inhibitory Effect of Polyunsaturated Fatty Acids on MMP-9 Release from Microglial Cells—Implications for Complementary Multiple Sclerosis Treatment

Liuzzi, Grazia Maria; Latronico, Tiziana; Rossano, Rocco; Viggiani, Sandra; Fasano, A.; Riccio, P.

doi:10.1007/s11064-007-9415-9

Cited by 44 publications

(32 citation statements)

References 50 publications

(52 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Considering the relevance of blood-brain barrier integrity in MS physiopathology, Liuzzi et al (2007) demonstrated that the in vitro treatment of microglia with omega-3 PUFAs decreases the LPS-induced production of matrix metalloproteinase-9, which is involved in the mechanism of blood-brain barrier disruption, the penetration of inflammatory cells into the CNS, and, consequently, demyelination.…”

Section: Demyelination/remyelination and Nutrientsmentioning

confidence: 99%

Nutritional factors and aging in demyelinating diseases

Adamo

2013

Genes Nutr

View full text Add to dashboard Cite

Demyelination is a pathological process characterized by the loss of myelin around axons. In the central nervous system, oligodendroglial damage and demyelination are common pathological features characterizing white matter and neurodegenerative disorders. Remyelination is a regenerative process by which myelin sheaths are restored to demyelinated axons, resolving functional deficits. This process is often deficient in demyelinating diseases such as multiple sclerosis (MS), and the reasons for the failure of repair mechanisms remain unclear. The characterization of these mechanisms and the factors involved in the proliferation, recruitment, and differentiation of oligodendroglial progenitor cells is key in designing strategies to improve remyelination in demyelinating disorders. First, a very dynamic combination of different molecules such as growth factors, cytokines, chemokines, and different signaling pathways is tightly regulated during the remyelination process. Second, factors unrelated to this pathology, i.e., age and genetic background, may impact disease progression either positively or negatively, and in particular, age-related remyelination failure has been proven to involve oligodendroglial cells aging and their intrinsic capacities among other factors. Third, nutrients may either help or hinder disease progression. Experimental evidence supports the anti-inflammatory role of omega-6 and omega-3 polyunsaturated fatty acids through the competitive inhibition of arachidonic acid, whose metabolites participate in inflammation, and the reduction in T cell proliferation. In turn, vitamin D intake and synthesis have been associated with lower MS incidence levels, while vitamin D-gene interactions might be involved in the pathogenesis of MS. Finally, dietary polyphenols have been reported to mitigate demyelination by modulating the immune response.

show abstract

Section: Demyelination/remyelination and Nutrientsmentioning

confidence: 99%

Nutritional factors and aging in demyelinating diseases

Adamo

2013

Genes Nutr

View full text Add to dashboard Cite

show abstract

“…Microglia are constantly moving and analyzing the CNS for damaged neurons, plaques, and infectious agents [1][2][3]. Since this process must be quickly done to prevent fatal damage potentially, microglia are extremely sensitive to even small pathological changes in the CNS [4].…”

Section: Introductionmentioning

confidence: 99%

Comparison of Ionized Calcium-binding Adapter Molecule 1-Immunoreactive Microglia in the Spinal Cord Between Young Adult and Aged Dogs

et al. 2009

View full text Add to dashboard Cite

Microglia are main form of active immune defense, and they are constantly moving and analyzing the CNS for damaged neurons and infectious agents. In this study, we compared microglia in the spinal cord of the young adult (1-2 years old) and aged (10-12 years old) German Shepherd dogs via immunohistochemistry and western blot analysis for ionized calcium-binding adapter molecule 1 (Iba-1), a microglial marker. In addition, we also observed the interferon-gamma (IFN-gamma), a pro-inflammatory cytokine, and interleukin-1beta (IL-1beta), produced by activated microglia/macrophage, protein levels in these groups. At first, we found that neuronal nuclei (NeuN, a neuronal marker)-immunoreactive neurons were distributed throughout the grey mate of the spinal cord, and there were no significant differences between the adult and aged groups. Most of Iba-1-immunoreactive microglia were morphologically ramified microglia (resting form) in the adult group, while some Iba-1-immunoreactive microglia were morphologically activated microglia in the aged group. In western blot analysis, Iba-1, IFN-gamma and IL-1beta expression were increased in the aged group. This result may be associated with age-dependent changes in the spinal cord.

show abstract

“…In particular, it has been demonstrated that ω3 PUFAs inhibited in vitro MMP-9 production in lipopolysaccharide-activated microglia. 10 The mechanisms by which ω3 PUFAs downregulate the production of MMPs may be related to their inhibitory effect on proinflammatory cytokines involved in the induction of MMPs, such as TNFα, IL-1 and IL-2. 49 However, it has been suggested that ω3 PUFAs may directly inhibit MMP gene transcription through their inhibitory effect on NFκB-and AP1-binding activity.…”

Section: Exogenous Natural Mmp Inhibitorsmentioning

confidence: 99%

“…4,5 Several studies have shown that both anti-MS-specific therapies [6][7][8][9] and some antioxidant and anti-inflammatory compounds have the ability to downregulate MMPs, suggesting that inhibition of MMPs may represent an additional mechanism by which these agents decrease the development of new CNS lesions in the course of MS. [10][11][12] In this review, we summarize the general characteristics of the different MMPs and their regulatory mechanisms. The pathogenic role of MMPs in the development and progression …”

Section: Introductionmentioning

confidence: 99%

Metalloproteinases and their inhibitors as therapeutic targets for multiple sclerosis: current evidence and future perspectives

Latronico¹,

Liuzzi²

2017

MNM

Self Cite

View full text Add to dashboard Cite

Abstract:The treatment of multiple sclerosis (MS) has seen important changes in the last two decades with the introduction of several drugs able to modify the evolution of this disease. Current MS therapies primarily target the peripheral immune response, although it has been suggested that their efficacy could be in part the result of the beneficial effect on other nonspecific targets, such as matrix metalloproteinases (MMPs). Numerous experimental studies have suggested that MMPs may be involved in MS pathogenesis by contributing to blood-brain barrier disruption, migration of leukocytes into the central nervous system, demyelination and axonal damage. Therefore, MMPs have been considered important therapeutic targets in the course of MS. In this respect, different attempts have been made to develop synthetic, low-molecular-weight inhibitors of MMPs for the potential treatment of diseases in which MMPs play a major role. However, technical difficulties, side effects and reduced patient compliance because of parenteral administration have greatly limited the development in the clinical practice of specific anti-MMP drugs. By contrast, interesting results have been obtained with compounds that are already used in the clinical practice, such as MS drugs and natural compounds with anti-inflammatory and antioxidant activity. Here, we discuss the evidence and potential mechanisms for altered MMP function in MS. Furthermore, we outline the possible medical implications for the use of compounds that target MMP activity and we propose that together with anti-MS drugs, other compounds with anti-inflammatory and antioxidant properties, such as natural ω3 fatty acids, polyphenols and tetracyclines, which inhibit MMP functions, might represent potential therapeutic approaches to mitigate MMP-related damage during MS.

show abstract

Inhibitory Effect of Polyunsaturated Fatty Acids on MMP-9 Release from Microglial Cells—Implications for Complementary Multiple Sclerosis Treatment

Cited by 44 publications

References 50 publications

Nutritional factors and aging in demyelinating diseases

Nutritional factors and aging in demyelinating diseases

Comparison of Ionized Calcium-binding Adapter Molecule 1-Immunoreactive Microglia in the Spinal Cord Between Young Adult and Aged Dogs

Metalloproteinases and their inhibitors as therapeutic targets for multiple sclerosis: current evidence and future perspectives

Contact Info

Product

Resources

About