Recent advances in understanding frontotemporal degeneration

Abstract

Frontotemporal degeneration (FTD) is a heterogeneous spectrum of neurodegenerative disorders characterized by diverse clinical presentations, neuropathological characteristics, and underlying genetic causes. In the last few years, several advances in the knowledge of clinical and biological aspects have been accomplished and three major scenarios have emerged that will represent the core issues in the FTD scene over the next few years. Foremost, the development of cerebrospinal fluid and blood biomarkers as well as neuroimaging techniques will aid the pursuit of new diagnostic and prognostic markers able to identify the ongoing proteinopathy and predict disease progression, which is key in identifying and stratifying patients for enrolment in clinical trials as well as evaluating response to treatment. On the other hand, current research has focused on the first attempts to slow down or revert disease progression, with the identification of disease modulators associated with disease onset and the ongoing development of the first pharmacological treatments for both sporadic and genetic FTD. Future research will certainly improve our knowledge of FTD and possibly open up a new era of disease-modifying therapies for this still-orphan disorder.

Hyaluronic acid synthesis, degradation, and crosslinking in equine osteoarthritis: TNF-α-TSG-6-mediated HC-HA formation

“…At least two studies have identified a link between SF TSG-6 levels and OA progression in human subjects [ 29 , 61 ], and others have demonstrated an increase in HC-HA complex formation in RA and in murine models of inflammatory arthritis [ 40 , 59 ]. Our finding that SF HA concentration and viscosity varied significantly between and among healthy and OA individuals supports the hypothesis that OA is a heterogenous disease that contains multiple endotypes that may progress differently and respond differently to various treatments [ 62 , 63 ].…”

New Horizons in Hydrogels for Methotrexate Delivery

“…MTX is a first-line disease-modifying drug proposed for treating the inflammatory forms of arthritis [ 88 ]. Rheumatoid arthritis (RA) and osteoarthritis (OA) are one of the leading forms of arthritic diseases, causing global disability [ 89 ], where RA is a chronic autoimmune disease and OA has been considered as a load-bearing disease, with low-grade inflammation [ 90 , 91 , 92 ]. MTX is the initial preferred drug for rheumatic diseases and is considered to be the gold standard for treatment of RA, used for more than three decades [ 93 ], however, it has been also proposed for treating OA [ 94 ].…”

Experimental Disease-Modifying Agents for Frontotemporal Lobar Degeneration

“…3 The occurrence of associated motor symptoms, as in progressive supranuclear palsy (PSP), corticobasal syndrome (CBS) and motor neuron disease (FTD-MND), enriches the spectrum of FTDrelated disorders. 4 Common to all FTD clinical syndromes is the underlying frontotemporal lobar degeneration (FTLD) which can be classified according to the predominant constituent proteins of cellular inclusions. While until 2006 only FTLD-Tau was well characterized, the following discovery of TAR DNA binding protein 43 (TDP- 43) and FET family proteins within tau-negative, ubiquitin-positive inclusions of a vast majority of FTLD cases, led to the introduction, respectively, of FTLD-TDP and FTLD-FET neuropathology.…”

“… 3 The occurrence of associated motor symptoms, as in progressive supranuclear palsy (PSP), corticobasal syndrome (CBS) and motor neuron disease (FTD-MND), enriches the spectrum of FTD-related disorders. 4 …”