Cellular mechanisms of fibrin (ogen): insight from neurodegenerative diseases

Abstract

Neurodegenerative diseases are prevalent and currently incurable conditions that progressively impair cognitive, behavioral, and psychiatric functions of the central or peripheral nervous system. Fibrinogen, a macromolecular glycoprotein, plays a crucial role in the inflammatory response and tissue repair in the human body and interacts with various nervous system cells due to its unique molecular structure. Accumulating evidence suggests that fibrinogen deposits in the brains of patients with neurodegenerative diseases. By regulating pathophysiological mechanisms and signaling pathways, fibrinogen can exacerbate the neuro-pathological features of neurodegenerative diseases, while depletion of fibrinogen contributes to the amelioration of cognitive function impairment in patients. This review comprehensively summarizes the molecular mechanisms and biological functions of fibrinogen in central nervous system cells and neurodegenerative diseases, including Alzheimer’s disease, Multiple Sclerosis, Parkinson’s disease, Vascular dementia, Huntington’s disease, and Amyotrophic Lateral Sclerosis. Additionally, we discuss the potential of fibrinogen-related treatments in the management of neurodegenerative disorders.

Fibrinogen is the key factor associated with tremor relieve and recurrence in the ET patients subjected with unilateral MRgFUS thalamotomy

“…More and more studies are beginning to emphasize its unique molecular structure, which contains multiple binding sites for receptors and proteins, resulting in a pluralistic signaling network and pleiotropic functions in neurological disease [24]. For example, in neurodegenerative diseases, fibrinogen not only provides binding sites for toxic substances (such as Aβ and α-synuclein) [25], but also induces microglial activation via CD11b/CD18 to promote initial neuroinflammatory [25]. An overdose of fibrinogen can also hinder neurite outgrowth by acting as a ligand for the β3 integrin receptor on neurons [26], and stimulates the generation of reactive oxygen species and mitochondrial superoxide which causing apoptosis and death [27].…”

“…It has been well proven that the ultrasound transmission is closely related to the medium characteristics. Long-term hypertension can lead to microcirculation dysfunction [24], which subsequently leads to the alteration in gray matter microstructure [25], the overload of cerebral blood flow and cerebrospinal fluid circulation [26]. These alterations can be sensitively captured in diagnostic ultrasound such as time-harmonic ultrasound elastography, so whether there is an impact on high-intensity focused ultrasound is currently unclear.…”

Circulating microRNA miR-425-5p Associated with Brain White Matter Lesions and Inflammatory Processes

“…As previous research suggests a prominent role of inflammation in the development of neurological diseases [18,19] and involvement of hsa-miR-425-5p in microglia inflammation in a mouse stroke model [20], we examined the association between hsa-miR-425-5p and the blood-based inflammation markers CRP and fibrinogen. Both inflammation markers were negatively associated with the abundance of hsa-miR-425-5p (p CRP = 0.026, p FIB = 0.001).…”

Dosimetry of [64Cu]FBP8: a fibrin-binding PET probe

“…In multiple sclerosis, extravascular fibrin has been proposed as a driver of neuroinflammation [6]. In Alzheimer's disease, extravascular fibrin is linked to higher inflammation, neuronal loss and cognitive decline [7]. Extravascular fibrin is also present in most solid tumors [8].…”