Implications of VIP and PACAP in Parkinson's Disease: What do we Know So Far?

BACKGROUND: Parkinson's disease is one of the most common neurodegenerative disorders and although its aetiology is not yet fully understood, neuroinflammation has been identified as a key factor in the progression of the disease. Vasoactive intestinal peptide and pituitary adenylate-cyclase activating polypeptide are two neuropeptides that exhibit anti-inflammatory and neuroprotective properties, modulating the production of cytokines and chemokines and the behaviour of immune cells. However, the role of chemokines and cytokines modulated by the endogenous receptors of the peptides varies according to the stage of the disease. METHODS: We present an overview of the relationship between some cytokines and chemokines with vasoactive intestinal peptide, pituitary adenylate cyclase activating polypeptide and their endogenous receptors in the context of Parkinson's disease neuroinflammation and oxidative stress, as well as the modulation of microglial cells by the peptides in this context. RESULTS: The two peptides exhibit neuroprotective and anti-inflammatory properties in models of Parkinson's disease, as they ameliorate cognitive functions, decrease the level of neuroinflammation and promote dopaminergic neuronal survival. The peptides have been tested in a variety of in vivo and in vitro models of Parkinson's disease, demonstrating the potential for therapeutic application. CONCLUSION: More studies are needed to establish the clinical use of vasoactive intestinal peptide and pituitary adenylate cyclase activating polypeptide as safe candidates for treating Parkinson's disease, as the use of the peptides in different stages of the disease could produce different results concerning effectiveness.

Papel da MMP-8 na doença periodontal / MMP-8 E periodontal disease

As metaloproteinases da matriz (MMP) e os inibidores de metaloproteinase da matriz (TIMP) são enzimas extremamente importantes na remodelação do tecido conjuntivo durante o desenvolvimento, homeostase e cicatrização. O desequilibrio entre as MMPs ativadas e seus inibidores endógenos leva ao colapso patológico da matriz extracelular durante a doença periodontal provocando a degradação das fibras colágenas inseridas na raiz e a migração apical do epitélio com formação da bolsa periodontal. A MMP-8 destaca-se entre as MMPs predominantemente presentes no tecido gengival inflamado, fluido gengival crevicular e saliva bem como fluido sulcular e peri-implantar. O nível e grau de ativação desta enzima parecem aumentar com o aumento da atividade e gravidade da doença periodontal e diminuir em seguida ao tratamento. Diante da importância dessa enzima na evolução da doença periodontal, esse trabalho teve como objetivo desenvolver uma revisão de literatura sobre o papel da MMP- 8 e do seu principal inibidor, TIMP-1, na degradação de colágeno gengival durante a doença periodontal, destacando suas características, mecanismo de ação e inibição, expressão tecidual e níveis no fluido gengival crevicular.

Matrix metaloproteinase (MMP) and tissue inhibitor of matrix metalloproteinase (TIMP) are extremely important enzymes in connective tissue remodeling during development, homeostasis and healing. An imbalancebetween active MMPs and TIMPs create a pathological collapse of extracellular matrix during periodontal disease generating degradation of collagen fibers attached to the root surface and epithelial apical migration with pocket formation. MMP-8 is the major class among MMPs observed in inflammed gingival tissue, gingival crevicular fluid, saliva as well as dental and peri-implantar sulcular fluid. The levels and activation of this enzyme seems to increase with the activity and severity of periodontal disease, and decrease after treatment. Due to MMP-8 relevance in periodontal disease development, this paper aimed to review MMP-8 and TIMP-1 participation in gingival collagen degradation during periodontal disease, underlining the enzyme characteristics, action and inhibition mechanisms, tissular expression and gingival crevicular fluid levels.